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Trilaciclib (G1T28) in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02514447
Collaborator
(none)
123
Enrollment
50
Locations
9
Arms
72
Actual Duration (Months)
2.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.

The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).

Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).

The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher.

The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report.

The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off [DCO] for Primary Completion Date [PCD] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021).

The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.

Study Design

Study Type:
Interventional
Actual Enrollment :
123 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Previously Treated Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy
Actual Study Start Date :
Oct 5, 2015
Actual Primary Completion Date :
Sep 28, 2018
Actual Study Completion Date :
Oct 4, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b

Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).

Drug: Placebo

Drug: Topotecan
Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a

Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

Drug: Trilaciclib
Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b

    Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1

    Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1

    Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1

    Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1

    Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1

    Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan
    Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1

    Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).

    Drug: Trilaciclib
    Other Names:
  • G1T28
  • CDK 4/6 inhibitor

    • Drug: Topotecan

    Outcome Measures

    Primary Outcome Measures

    1. Duration of Severe (Grade 4) Neutropenia in Cycle 1 [Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)]

      Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10^9/L and (2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.

    2. Occurrence of Severe (Grade 4) Neutropenia [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.

    3. Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 [Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days)]

      The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days ≥ Grade 3 neutropenic infection/febrile neutropenia Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)

    Secondary Outcome Measures

    1. Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan [Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.]

      Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan

    2. Progression Free Survival (PFS) [From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days).]

      Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause. Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    3. Overall Survival (OS) [From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days).]

      Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.

    4. Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      The weekly event rate of Major Adverse Hematologic Events (MAHE) events

    5. Tumor Response Based on RECIST, Version 1.1 [From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).]

      The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.

    6. Occurrence of RBC Transfusions [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days).]

      Percentage of patients requiring a RBC transfusion on/after week 5

    7. Need for Treatment With Hematopoietic Growth Factors [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients requiring G-CSF administration.

    8. Chemotherapy Cycles and Modifications Overall [During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).]

      Average exposure and cycle modifications in chemotherapy (topotecan)

    9. Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) [Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.]

      Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)

    10. Duration of Response (DOR) [From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).]

      The median months and 95% CIs of duration of response.

    11. Occurrence of Intravenous (IV) Antibiotic Use [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients requiring systemic/IV antibiotics

    12. Occurrence of Platelet Transfusions [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients requiring a platelet transfusion

    13. Occurrence of Febrile Neutropenia Adverse Events [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients who experience febrile neutropenia adverse events

    14. Occurrence of Infection Serious Adverse Events (SAEs) [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations

    15. Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)

    16. Dose Reductions in Chemotherapy (Topotecan) [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      Overall event rate of dose reductions in chemotherapy (topotecan)

    17. Occurrence of Grade 3 and 4 Hematologic Toxicities [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.

    18. Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).

    19. Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations [During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).]

      The count of patients who received any ESA administration.

    20. Chemotherapy Exposure [During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).]

      Average duration of exposure to chemotherapy (topotecan) in days.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Male or female subjects aged ≥18 years

    • Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry

    • Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy

    • At least 1 target lesion that is measurable by RECIST, Version 1.1

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2

    • Adequate organ function

    Key Exclusion Criteria:

    • Presence of brain metastases requiring immediate treatment with radiation therapy or steroids.

    • Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure

    • Known history of stroke or cerebrovascular accident within 6 months prior to enrollment

    • Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol

    • Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites

    • Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment

    • History of topotecan treatment for SCLC

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Genesis Cancer Center Hot Springs Arkansas United States 71913
    2 Highlands Oncology Group Rogers Arkansas United States 72758
    3 Compassionate Cancer Care Medical Group, Inc. Corona California United States 92879
    4 Sutter Medical Group Sacramento California United States 95816
    5 The Oncology Institute of Hope and Innovation Whittier California United States 90603
    6 Memorial Hospital - University of Colorado Health Colorado Springs Colorado United States 80909
    7 Rocky Mountain Cancer Centers Denver Colorado United States 80218
    8 University of Colorado Health, Oncology Clinical Research Northern Region Fort Collins Colorado United States 80528
    9 Florida Cancer Specialists - South Fort Myers Florida United States 33916
    10 Florida Cancer Specialists - North Tavares Florida United States 32778
    11 University Cancer and Blood Center, LLC Athens Georgia United States 30607
    12 Emory University Atlanta Georgia United States 30322
    13 Northside Hospital - Georgia Cancer Specialists Atlanta Georgia United States 30341
    14 Saint Luke's Cancer Institute Kansas City Missouri United States 64111
    15 Norris Cotton Cancer Center Lebanon New Hampshire United States 03756
    16 North Shore Hematology Oncology Associates PC East Setauket New York United States 11733
    17 Regional Medical Oncology Center Wilson North Carolina United States 27893
    18 Gabrail Cancer Center Canton Ohio United States 44718
    19 Oklahoma University - Peggy and Charles Stephenson Cancer Center Oklahoma City Oklahoma United States 73117
    20 Guthrie Medical Group, PC Sayre Pennsylvania United States 18840
    21 AnMed Health Anderson South Carolina United States 29621
    22 Greenville Health System Greenville South Carolina United States 29605
    23 Gibbs Cancer Center Spartanburg South Carolina United States 29303
    24 Hanna Cancer Associates - University of Tennessee Knoxville Tennessee United States 37920
    25 Meharry Medical College Nashville Tennessee United States 37208
    26 Sarah Cannon Research Institute Nashville Tennessee United States 37232
    27 Texas Oncology- Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    28 M.D. Anderson Houston Texas United States 77030
    29 Millennium Oncology Houston Texas United States 77090
    30 Southwest Cancer Center Lubbock Texas United States 79415
    31 Texas Oncology Tyler Texas United States 75702
    32 The University of Texas Health Science Center at Tyler Tyler Texas United States 75708
    33 Virginia Cancer Specialists Fairfax Virginia United States 22031
    34 Virginia Oncology Associates Norfolk Virginia United States 23502
    35 Northwest Cancer Specialists, P.C. Vancouver Washington United States 98684
    36 AZ Klina Brasschaat Belgium 2930
    37 University Clinical Centre Banja Luka Banja Luka Bosnia and Herzegovina 78000
    38 University Clinical Centre Sarajevo Sarajevo Bosnia and Herzegovina 71000
    39 Clinical Hospital Centre Osijek Osijek Croatia 31000
    40 University Clinical Hospital Centre " Sestre Milosrdnice" Zagreb Croatia 10000
    41 University Hospital Centre Zagreb, Clinic For Pulmonary Diseases Jordanovac Zagreb Croatia 10000
    42 University Clinic of Radiotherapy and Oncology Skopje Skopje North Macedonia 1000
    43 Clinic for Pulmology, Clinical Centre of Serbia Belgrade Serbia 11000
    44 Clinical Hospital Centre Bezanijska Kosa Belgrade Serbia 11000
    45 Oncology and Radiology Institute of Serbia Belgrade Serbia 11000
    46 Clinical Center Nis, Clinic for Lung Diseases Nis Serbia 18204
    47 Institute for Pulmonary Diseases of Vojvodina Clinic for Thoracic Oncology Sremska Kamenica Serbia 21204
    48 VOU Department of Radiotherapy and Oncology Kosice Slovakia 04191
    49 POKO POPRAD, s.r.o. Poprad Slovakia 05801
    50 University Clinic of Respiratory and Allergic Diseases Golnik Golnik Slovenia

    Sponsors and Collaborators

    • G1 Therapeutics, Inc.

    Investigators

    • Study Director: Clinical Contact, G1 Therapeutics, Inc.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02514447
    Other Study ID Numbers:
    • G1T28-03
    • 2016-004611-13
    First Posted:
    Aug 3, 2015
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by G1 Therapeutics, Inc.
    SCLC
    CDK4/6 Inhibitor
    Additional relevant MeSH terms:
    Lung Neoplasms
    Small Cell Lung Carcinoma
    Topotecan

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebo Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Period Title: Overall Study
    STARTED 29 30 32 2 3 4 8 7 8
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 29 30 32 2 3 4 8 7 8

    Baseline Characteristics

    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 Total
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²). Total of all reporting groups
    Overall Participants 29 30 32 2 3 4 8 7 8 123
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    18
    62.1%
    18
    60%
    20
    62.5%
    1
    50%
    1
    33.3%
    1
    25%
    6
    75%
    4
    57.1%
    2
    25%
    71
    57.7%
    >=65 years
    11
    37.9%
    12
    40%
    12
    37.5%
    1
    50%
    2
    66.7%
    3
    75%
    2
    25%
    3
    42.9%
    6
    75%
    52
    42.3%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    64
    (8.1)
    63
    (8.2)
    62
    (7.3)
    66
    (9.2)
    69
    (9.1)
    71
    (6.1)
    62
    (8.4)
    63
    (8.9)
    69
    (10.4)
    64
    (8.2)
    Sex: Female, Male (Count of Participants)
    Female
    17
    58.6%
    14
    46.7%
    10
    31.3%
    0
    0%
    2
    66.7%
    0
    0%
    5
    62.5%
    0
    0%
    4
    50%
    52
    42.3%
    Male
    12
    41.4%
    16
    53.3%
    22
    68.8%
    2
    100%
    1
    33.3%
    4
    100%
    3
    37.5%
    7
    100%
    4
    50%
    71
    57.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    28
    96.6%
    30
    100%
    31
    96.9%
    2
    100%
    3
    100%
    4
    100%
    8
    100%
    7
    100%
    8
    100%
    121
    98.4%
    Unknown or Not Reported
    1
    3.4%
    0
    0%
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    3.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    6.9%
    0
    0%
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    1
    12.5%
    1
    14.3%
    1
    12.5%
    6
    4.9%
    White
    26
    89.7%
    29
    96.7%
    30
    93.8%
    2
    100%
    3
    100%
    4
    100%
    7
    87.5%
    6
    85.7%
    7
    87.5%
    114
    92.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    3.4%
    0
    0%
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.6%
    Region of Enrollment (participants) [Number]
    United States
    18
    62.1%
    27
    90%
    14
    43.8%
    2
    100%
    3
    100%
    4
    100%
    8
    100%
    7
    100%
    8
    100%
    91
    74%
    Serbia
    11
    37.9%
    3
    10%
    12
    37.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    26
    21.1%
    Belgium
    0
    0%
    0
    0%
    1
    3.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    North Macedonia
    0
    0%
    0
    0%
    2
    6.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.6%
    Croatia
    0
    0%
    0
    0%
    3
    9.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    2.4%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    Grade 0-1
    27
    93.1%
    27
    90%
    29
    90.6%
    2
    100%
    3
    100%
    4
    100%
    6
    75%
    7
    100%
    7
    87.5%
    112
    91.1%
    Grade 2
    2
    6.9%
    3
    10%
    3
    9.4%
    0
    0%
    0
    0%
    0
    0%
    2
    25%
    0
    0%
    1
    12.5%
    11
    8.9%
    Body Weight at Screening (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    72.7
    (16.37)
    71.9
    (17.08)
    75.7
    (17.28)
    95.2
    (22.20)
    72.6
    (23.59)
    90.1
    (23.05)
    73.5
    (29.88)
    86.3
    (19.25)
    67.8
    (15.00)
    74.7
    (18.55)
    Height at Screening (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    166.2
    (9.85)
    169.0
    (9.49)
    172.2
    (10.01)
    176.2
    (1.27)
    169.7
    (18.53)
    175.3
    (5.42)
    165.2
    (12.93)
    175.3
    (3.49)
    167.4
    (16.74)
    169.5
    (10.56)
    BMI at Screening (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    26.13
    (4.239)
    25.04
    (4.820)
    25.43
    (5.113)
    30.72
    (7.595)
    24.63
    (2.430)
    29.05
    (6.218)
    26.06
    (7.164)
    28.11
    (6.232)
    24.15
    (3.502)
    25.79
    (4.984)
    Body Surface Area at Screening (m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m^2]
    1.80
    (0.234)
    1.81
    (0.234)
    1.88
    (0.234)
    2.11
    (0.200)
    1.83
    (0.398)
    2.05
    (0.282)
    1.79
    (0.398)
    2.01
    (0.185)
    1.76
    (0.274)
    1.85
    (0.255)

    Outcome Measures

    1. Primary Outcome
    Title Duration of Severe (Grade 4) Neutropenia in Cycle 1
    Description Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10^9/L and (2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
    Time Frame Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebo Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Mean (Standard Deviation) [days]
    8
    (6.0)
    1
    (3.1)
    2
    (3.9)
    14
    (1.4)
    8
    (6.8)
    0
    (0)
    0
    (0)
    2
    (3.6)
    3
    (5.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b
    Comments Analysis was for Part 2 data: Treatment difference was evaluated using a nonparametric analysis of covariance (ANCOVA). The nonparametric ANCOVA included study baseline ANC value as covariate, stratification factors of ECOG performance status (0 to 1 versus 2) and sensitivity to first line treatment (sensitive or resistant) and treatment as fixed effects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments A Hochberg-based gatekeeping procedure was used to control the global familywise error rate across the multiple null hypotheses (primary and key secondary myelosuppression efficacy endpoints) in a strong sense at a 1-sided 0.10 level.
    Method non-parametric ANCOVA
    Comments Hochberg-based gatekeeping procedure
    2. Primary Outcome
    Title Occurrence of Severe (Grade 4) Neutropenia
    Description Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    22
    75.9%
    5
    16.7%
    13
    40.6%
    2
    100%
    2
    66.7%
    1
    25%
    0
    0%
    2
    28.6%
    3
    37.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b, Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b
    Comments The occurrence of SN was a binary variable. Treatment group difference was analyzed using modified Poisson regression to account for the variable duration of the Treatment Period for each patient. The model included baseline ANC as a covariate, stratification factors of ECOG performance status (0 or 1 vs 2), sensitivity to 1st line treatment (sensitive or resistant), and treatment as fixed effects. The logarithm transformation of # of cycles was included as an offset variable in the modeling.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0160
    Comments A Hochberg-based gatekeeping procedure was used to control the global familywise error rate across the multiple null hypotheses (primary and key secondary myelosuppression efficacy endpoints) in a strong sense at a 1-sided 0.10 level.
    Method Modified Poisson
    Comments Hochberg-based gatekeeping procedure
    3. Primary Outcome
    Title Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1
    Description The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days ≥ Grade 3 neutropenic infection/febrile neutropenia Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)
    Time Frame Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set: All enrolled patients who received at least 1 dose of study drug.
    Arm/Group Title Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m²- Part 1 Cohort 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m²- Part 1 Cohort 2 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m²- Part 1 Cohort 3 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m²- Part 1 Cohorts 4 and 6 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m²- Part 1 Cohort 5 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m²- Part 1 Cohort 7
    Arm/Group Description Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan
    Measure Participants 2 3 4 8 7 8
    Count of Participants [Participants]
    2
    6.9%
    2
    6.7%
    2
    6.3%
    0
    0%
    2
    66.7%
    2
    50%
    4. Secondary Outcome
    Title Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan
    Description Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan
    Time Frame Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.

    Outcome Measure Data

    Analysis Population Description
    All patients who had evaluable PK profiles for both treatments and analytes.
    Arm/Group Title Trilaciclib (G1T28) 200 mg/m² + Topotecan - Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan - Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan - Part 1 Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b
    Arm/Group Description Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan
    Measure Participants 9 15 7 0 28 30
    Geometric Mean (Geometric Coefficient of Variation) [ng/ml]
    1060
    (59.0)
    1220
    (120)
    2220
    (75.2)
    913
    (59.6)
    1100
    (54.8)
    5. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause. Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
    Time Frame From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Median (95% Confidence Interval) [months]
    4.2
    3.0
    4.2
    5.5
    4.3
    3.6
    4.5
    1.8
    2.1
    6. Secondary Outcome
    Title Overall Survival (OS)
    Description Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.
    Time Frame From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Median (95% Confidence Interval) [months]
    6.5
    5.8
    6.2
    NA
    10.6
    8.3
    9.4
    4.4
    10.0
    7. Secondary Outcome
    Title Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan
    Description The weekly event rate of Major Adverse Hematologic Events (MAHE) events
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Number [events per participant/week]
    0.258
    0.091
    0.102
    0.403
    0.156
    0.102
    0.037
    0.085
    0.073
    8. Secondary Outcome
    Title Tumor Response Based on RECIST, Version 1.1
    Description The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.
    Time Frame From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).

    Outcome Measure Data

    Analysis Population Description
    Response-Evaluable analysis set: All patients who are in the mITT, have measurable disease (target lesions) at the baseline tumor assessment, and either (i) have at least 1 post-baseline tumor assessment, (ii) have clinical progression as noted by the investigator before their first post-baseline tumor scan, or (iii) have died due to disease progression before their first post-baseline tumor scan.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 26 29 30 2 3 4 8 6 7
    Complete Response (CR)
    1
    3.4%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Partial Response (PR)
    5
    17.2%
    3
    10%
    5
    15.6%
    1
    50%
    2
    66.7%
    0
    0%
    1
    12.5%
    0
    0%
    1
    12.5%
    Stable Disease (SD)
    10
    34.5%
    15
    50%
    13
    40.6%
    1
    50%
    0
    0%
    3
    75%
    6
    75%
    3
    42.9%
    3
    37.5%
    Progressive Disease (PD)
    6
    20.7%
    9
    30%
    6
    18.8%
    0
    0%
    1
    33.3%
    1
    25%
    1
    12.5%
    2
    28.6%
    2
    25%
    Not Evaluable (NE)
    2
    6.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    No post-baseline tumor assessment (Missing)
    2
    6.9%
    2
    6.7%
    6
    18.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    1
    12.5%
    9. Secondary Outcome
    Title Occurrence of RBC Transfusions
    Description Percentage of patients requiring a RBC transfusion on/after week 5
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    12
    41.4%
    5
    16.7%
    10
    31.3%
    2
    100%
    1
    33.3%
    2
    50%
    1
    12.5%
    1
    14.3%
    2
    25%
    10. Secondary Outcome
    Title Need for Treatment With Hematopoietic Growth Factors
    Description Percentage of patients requiring G-CSF administration.
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    19
    65.5%
    8
    26.7%
    16
    50%
    2
    100%
    2
    66.7%
    1
    25%
    4
    50%
    2
    28.6%
    3
    37.5%
    11. Secondary Outcome
    Title Chemotherapy Cycles and Modifications Overall
    Description Average exposure and cycle modifications in chemotherapy (topotecan)
    Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set: All enrolled patients who received at least 1 dose of study drug.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 28 30 32 2 3 4 8 7 8
    Number of cycles completed
    4
    (3.4)
    5
    (5.4)
    5
    (4.4)
    6
    (0.0)
    7
    (5.0)
    4
    (1.7)
    6
    (2.9)
    4
    (3.4)
    4
    (2.2)
    Number of cycles delayed
    1
    (1.2)
    2
    (2.5)
    1
    (1.4)
    3
    (1.4)
    1
    (1.2)
    1
    (0.5)
    1
    (0.8)
    0
    (0.5)
    1
    (1.0)
    12. Secondary Outcome
    Title Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28)
    Description Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)
    Time Frame Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose.

    Outcome Measure Data

    Analysis Population Description
    All patients who had evaluable PK profiles for both treatments and analytes.
    Arm/Group Title Trilaciclib (G1T28) + Topotecan 0.75 mg/m²- Part 1 Trilaciclib (G1T28) + Topotecan 1 mg/m²- Part 1 Trilaciclib (G1T28) + Topotecan 1.25 mg/m²- Part 1 Trilaciclib (G1T28) + Topotecan 1.50 mg/m²- Part 1 Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b
    Arm/Group Description Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75, 1.0, 1.25, or 1.50 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200, 240, or 280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan
    Measure Participants 19 7 3 2 25 27 29
    Geometric Mean (Geometric Coefficient of Variation) [ng/ml]
    21.1
    (34.6)
    36.8
    (41.8)
    52.4
    (66.5)
    NA
    (NA)
    43.0
    (39.0)
    17.5
    (36.5)
    41.4
    (46.9)
    13. Secondary Outcome
    Title Duration of Response (DOR)
    Description The median months and 95% CIs of duration of response.
    Time Frame From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days).

    Outcome Measure Data

    Analysis Population Description
    Response-Evaluable analysis set: All patients who are in the mITT, have measurable disease (target lesions) at the baseline tumor assessment, and either (i) have at least 1 post-baseline tumor assessment, (ii) have clinical progression as noted by the investigator before their first post-baseline tumor scan, or (iii) have died due to disease progression before their first post-baseline tumor scan.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 6 3 5 1 2 0 1 0 1
    Median (95% Confidence Interval) [months]
    4.9
    7.8
    6.8
    NA
    5.4
    6.7
    NA
    14. Secondary Outcome
    Title Occurrence of Intravenous (IV) Antibiotic Use
    Description Percentage of patients requiring systemic/IV antibiotics
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    8
    27.6%
    8
    26.7%
    7
    21.9%
    2
    100%
    1
    33.3%
    1
    25%
    1
    12.5%
    2
    28.6%
    1
    12.5%
    15. Secondary Outcome
    Title Occurrence of Platelet Transfusions
    Description Percentage of patients requiring a platelet transfusion
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    9
    31%
    4
    13.3%
    8
    25%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    16. Secondary Outcome
    Title Occurrence of Febrile Neutropenia Adverse Events
    Description Percentage of patients who experience febrile neutropenia adverse events
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    5
    17.2%
    1
    3.3%
    2
    6.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    17. Secondary Outcome
    Title Occurrence of Infection Serious Adverse Events (SAEs)
    Description Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    3
    10.3%
    2
    6.7%
    1
    3.1%
    2
    100%
    1
    33.3%
    1
    25%
    0
    0%
    0
    0%
    1
    12.5%
    18. Secondary Outcome
    Title Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)
    Description Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    1
    3.4%
    1
    3.3%
    1
    3.1%
    1
    50%
    1
    33.3%
    1
    25%
    0
    0%
    0
    0%
    1
    12.5%
    19. Secondary Outcome
    Title Dose Reductions in Chemotherapy (Topotecan)
    Description Overall event rate of dose reductions in chemotherapy (topotecan)
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Number [events per participant per cycle]
    0.116
    0.053
    0.051
    0.500
    0.250
    0.118
    0.089
    0.040
    0.036
    20. Secondary Outcome
    Title Occurrence of Grade 3 and 4 Hematologic Toxicities
    Description The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    27
    93.1%
    25
    83.3%
    29
    90.6%
    2
    100%
    3
    100%
    4
    100%
    7
    87.5%
    7
    100%
    7
    87.5%
    21. Secondary Outcome
    Title Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia)
    Description The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Overall Grade 3/4 Thrombocytopenia
    19
    65.5%
    15
    50%
    21
    65.6%
    2
    100%
    2
    66.7%
    3
    75%
    2
    25%
    4
    57.1%
    4
    50%
    Overall Grade 4 Thrombocytopenia
    11
    37.9%
    9
    30%
    13
    40.6%
    2
    100%
    1
    33.3%
    2
    50%
    0
    0%
    2
    28.6%
    1
    12.5%
    22. Secondary Outcome
    Title Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations
    Description The count of patients who received any ESA administration.
    Time Frame During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days).

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) analysis set: All enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 29 30 32 2 3 4 8 7 8
    Count of Participants [Participants]
    6
    20.7%
    5
    16.7%
    1
    3.1%
    2
    100%
    1
    33.3%
    0
    0%
    1
    12.5%
    0
    0%
    1
    12.5%
    23. Secondary Outcome
    Title Chemotherapy Exposure
    Description Average duration of exposure to chemotherapy (topotecan) in days.
    Time Frame During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days).

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set: All enrolled patients who received at least 1 dose of study drug.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    Measure Participants 28 30 32 2 3 4 8 7 8
    Mean (Standard Deviation) [days]
    94
    (75.9)
    110
    (132.1)
    109
    (97)
    147
    (9.9)
    147
    (116.9)
    102
    (38.9)
    124
    (65.8)
    78
    (74.9)
    83
    (51.8)

    Adverse Events

    Time Frame The SAE reporting period started at the time of informed consent and the AE reporting period started from the time of first dose of study drug; both were assessed through 30 calendar days after the last administration of trilaciclib (G1T28) + topotecan (assessed up to a maximum of 1689 days). All-Cause Mortality was assessed from the date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2196 days).
    Adverse Event Reporting Description The safety analysis set (AEs and SAEs) includes all enrolled patients who received at least 1 dose of study drug (topotecan or trilaciclib/placebo). Analyses using the safety analysis set will be conducted on the basis of the actual treatment received. The intent-to-treat (ITT) analysis set (All-Cause Mortality) includes all enrolled patients who received at least one dose of study drugs in Part 1 and all randomized patients in Part 2 on the basis of the assigned treatment.
    Arm/Group Title Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Arm/Group Description Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Placebos Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
    All Cause Mortality
    Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/29 (82.8%) 28/30 (93.3%) 29/32 (90.6%) 0/2 (0%) 3/3 (100%) 4/4 (100%) 8/8 (100%) 6/7 (85.7%) 5/8 (62.5%)
    Serious Adverse Events
    Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/28 (25%) 15/30 (50%) 12/32 (37.5%) 2/2 (100%) 1/3 (33.3%) 2/4 (50%) 0/8 (0%) 1/7 (14.3%) 1/8 (12.5%)
    Blood and lymphatic system disorders
    Anemia 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 1/4 (25%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Febrile neutropenia 5/28 (17.9%) 6 1/30 (3.3%) 1 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Thrombocytopenia 1/28 (3.6%) 1 2/30 (6.7%) 2 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Leukopenia 0/28 (0%) 2/30 (6.7%) 4 0/32 (0%) 4 0/2 (0%) 4 0/3 (0%) 4 0/4 (0%) 4 0/8 (0%) 4 0/7 (0%) 4 0/8 (0%) 4
    Neutropenia 1/28 (3.6%) 2 0/30 (0%) 2 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Pancytopenia 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Cardiac disorders
    Myocardial infarction 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%)
    Cardiac arrest 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Atrial fibrillation 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Gastrointestinal disorders
    Duodenal ulcer perforation 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Dyspepsia 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Nausea 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Vomiting 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    General disorders
    Asthenia 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Infections and infestations
    Pneumonia 1/28 (3.6%) 1 1/30 (3.3%) 2 1/32 (3.1%) 1 1/2 (50%) 1 1/3 (33.3%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Bacteraemia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%)
    Lung infection 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%)
    Pneumonia pneumococcal 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%)
    Septic shock 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%)
    Sepsis 2/28 (7.1%) 3 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Injury, poisoning and procedural complications
    Fall 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%)
    Hip fracture 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Metabolism and nutrition disorders
    Hyponatraemia 0/28 (0%) 4/30 (13.3%) 7 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Failure to thrive 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Musculoskeletal and connective tissue disorders
    Muscular weakness 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%)
    Arthralgia 0/28 (0%) 1/30 (3.3%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Back pain 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Nervous system disorders
    Metabolic encephalopathy 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%)
    Seizure 0/28 (0%) 0/30 (0%) 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Cerebrovascular accident 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Syncope 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Transient ischaemic attack 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Renal and urinary disorders
    Haematuria 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 1/8 (12.5%) 2
    Pulmonary emobolism 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 1/4 (25%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Respiratory failure 0/28 (0%) 1/30 (3.3%) 2 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Acute respiratory failure 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Dyspnoea 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hypoxia 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Vascular disorders
    Thrombophlebitis 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Other (Not Including Serious) Adverse Events
    Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/28 (96.4%) 29/30 (96.7%) 32/32 (100%) 2/2 (100%) 3/3 (100%) 4/4 (100%) 8/8 (100%) 7/7 (100%) 8/8 (100%)
    Blood and lymphatic system disorders
    Neutropenia 23/28 (82.1%) 101 18/30 (60%) 58 24/32 (75%) 96 2/2 (100%) 19 3/3 (100%) 32 2/4 (50%) 7 5/8 (62.5%) 7 5/7 (71.4%) 14 5/8 (62.5%) 26
    Thrombocytopenia 19/28 (67.9%) 96 17/30 (56.7%) 65 20/32 (62.5%) 133 2/2 (100%) 47 3/3 (100%) 37 3/4 (75%) 18 1/8 (12.5%) 4 4/7 (57.1%) 17 3/8 (37.5%) 26
    Anaemia 24/28 (85.7%) 94 14/30 (46.7%) 55 17/32 (53.1%) 57 2/2 (100%) 35 3/3 (100%) 36 2/4 (50%) 5 3/8 (37.5%) 39 4/7 (57.1%) 11 6/8 (75%) 24
    Leukopenia 9/28 (32.1%) 36 7/30 (23.3%) 14 4/32 (12.5%) 7 2/2 (100%) 38 3/3 (100%) 54 1/4 (25%) 12 2/8 (25%) 35 2/7 (28.6%) 16 3/8 (37.5%) 49
    Febrile neutropenia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Lymphadenopathy 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Cardiac disorders
    Tachycardia 0/28 (0%) 0/30 (0%) 0/32 (0%) 2/2 (100%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Aortic valve incompetence 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Atrioventricular block first degree 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Atrioventricular block second degree 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Left ventricular hypertrophy 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 2 0/8 (0%) 2
    Sinus bradycardia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Sinus tachycardia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Supraventricular extrasystoles 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Tricuspid valve incompetence 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Ear and labyrinth disorders
    Tinnitus 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Endocrine disorders
    Hypothyroidism 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Eye disorders
    Vision blurred 0/28 (0%) 4/30 (13.3%) 4 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Diplopia 0/28 (0%) 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Eye discharge 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 1/3 (33.3%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Pupils unequal 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Visual impairment 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Gastrointestinal disorders
    Nausea 14/28 (50%) 21 16/30 (53.3%) 20 9/32 (28.1%) 18 0/2 (0%) 18 3/3 (100%) 3 2/4 (50%) 3 3/8 (37.5%) 3 4/7 (57.1%) 7 3/8 (37.5%) 4
    Diarrhoea 8/28 (28.6%) 13 7/30 (23.3%) 7 5/32 (15.6%) 7 1/2 (50%) 1 3/3 (100%) 5 1/4 (25%) 1 1/8 (12.5%) 1 1/7 (14.3%) 1 2/8 (25%) 5
    Vomiting 9/28 (32.1%) 11 4/30 (13.3%) 7 2/32 (6.3%) 7 0/2 (0%) 7 1/3 (33.3%) 1 1/4 (25%) 1 2/8 (25%) 3 0/7 (0%) 3 1/8 (12.5%) 1
    Constipation 3/28 (10.7%) 4 4/30 (13.3%) 4 2/32 (6.3%) 2 2/2 (100%) 2 2/3 (66.7%) 2 0/4 (0%) 2 2/8 (25%) 2 1/7 (14.3%) 1 4/8 (50%) 4
    Abdominal pain 2/28 (7.1%) 2 5/30 (16.7%) 8 1/32 (3.1%) 2 0/2 (0%) 2 1/3 (33.3%) 2 1/4 (25%) 1 1/8 (12.5%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Stomatitis 1/28 (3.6%) 1 0/30 (0%) 1 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Toothache 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Abdominal discomfort 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Dyspepsia 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Gastrooesophageal reflux disease 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 1 1/8 (12.5%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Flatulence 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Discomfort 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Abdominal pain upper 0/28 (0%) 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 4 0/8 (0%) 4
    Abdominal tenderness 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Oesophagitis 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Oral disorder 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 2 0/7 (0%) 2 0/8 (0%) 2
    Poor dental condition 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    General disorders
    Fatigue 10/28 (35.7%) 16 16/30 (53.3%) 22 13/32 (40.6%) 15 2/2 (100%) 3 3/3 (100%) 4 2/4 (50%) 2 4/8 (50%) 5 1/7 (14.3%) 3 4/8 (50%) 8
    Pyrexia 5/28 (17.9%) 6 2/30 (6.7%) 2 8/32 (25%) 8 1/2 (50%) 2 0/3 (0%) 2 2/4 (50%) 2 1/8 (12.5%) 1 1/7 (14.3%) 1 0/8 (0%) 0
    Asthenia 4/28 (14.3%) 4 5/30 (16.7%) 8 2/32 (6.3%) 3 2/2 (100%) 2 1/3 (33.3%) 1 1/4 (25%) 2 0/8 (0%) 2 2/7 (28.6%) 6 2/8 (25%) 3
    Non-cardiac chest pain 0/28 (0%) 7/30 (23.3%) 9 1/32 (3.1%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 2/8 (25%) 3
    Oedema peripheral 0/28 (0%) 5/30 (16.7%) 5 3/32 (9.4%) 3 1/2 (50%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Chest pain 0/28 (0%) 3/30 (10%) 3 0/32 (0%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 1/8 (12.5%) 2 0/7 (0%) 2 0/8 (0%) 2
    Chills 2/28 (7.1%) 3 0/30 (0%) 3 0/32 (0%) 3 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Malaise 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 2 1/7 (14.3%) 1 1/8 (12.5%) 1
    Gait disturbance 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Infusion site pain 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Infusion site reaction 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 1/3 (33.3%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Chest discomfort 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Face oedema 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 1/7 (14.3%) 1 0/8 (0%) 1
    Inflammation 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Influenza like illness 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Infusion site erythema 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Infusion site irritation 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Infusion site pruritus 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Mucosal inflammation 1/28 (3.6%) 1 0/30 (0%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 2 0/8 (0%) 2
    Pain 1/28 (3.6%) 1 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Peripheral swelling 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Infections and infestations
    Pneumonia 2/28 (7.1%) 2 1/30 (3.3%) 1 3/32 (9.4%) 3 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Upper respiratory tract infection 2/28 (7.1%) 2 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Urinary tract infection 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Cellulitis 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 2/3 (66.7%) 2 0/4 (0%) 2 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Bronchitis 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Herpes virus infection 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 2 0/7 (0%) 2 0/8 (0%) 2
    Herpes zoster 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Laryngitis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Nasopharyngitis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Oral candidiasis 1/28 (3.6%) 1 0/30 (0%) 1 1/32 (3.1%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Respiratory tract infection 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 4 0/2 (0%) 4 0/3 (0%) 4 0/4 (0%) 4 0/8 (0%) 4 1/7 (14.3%) 1 0/8 (0%) 1
    Rhinitis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Sinusitis 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Skin infection 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Subcutaneous abscess 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 2 0/7 (0%) 2 0/8 (0%) 2
    Injury, poisoning and procedural complications
    Fall 2/28 (7.1%) 2 2/30 (6.7%) 2 1/32 (3.1%) 1 1/2 (50%) 1 1/3 (33.3%) 1 1/4 (25%) 1 1/8 (12.5%) 2 0/7 (0%) 2 0/8 (0%) 2
    Contusion 0/28 (0%) 3/30 (10%) 3 0/32 (0%) 3 1/2 (50%) 1 1/3 (33.3%) 2 0/4 (0%) 2 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Skin abrasion 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Accidental overdose 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Infusion related reaction 0/28 (0%) 3/30 (10%) 3 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 1/8 (12.5%) 1
    Joint dislocation 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Joint injury 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Ligament sprain 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Lower limb fracture 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Scratch 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Investigations
    Neutrophil count decreased 1/28 (3.6%) 1 1/30 (3.3%) 1 2/32 (6.3%) 2 0/2 (0%) 2 1/3 (33.3%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 2
    Platelet count decreased 2/28 (7.1%) 2 1/30 (3.3%) 1 1/32 (3.1%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Blood lactate dehydrogenase increased 3/28 (10.7%) 6 0/30 (0%) 6 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Body temperature increased 0/28 (0%) 0/30 (0%) 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Weight decreased 2/28 (7.1%) 2 0/30 (0%) 2 1/32 (3.1%) 1 1/2 (50%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 2/7 (28.6%) 2 1/8 (12.5%) 1
    Alanine aminotransferase increased 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 1/2 (50%) 1 1/3 (33.3%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    International normalised ratio increased 2/28 (7.1%) 2 0/30 (0%) 2 0/32 (0%) 2 1/2 (50%) 6 0/3 (0%) 6 0/4 (0%) 6 0/8 (0%) 6 0/7 (0%) 6 0/8 (0%) 6
    Aspartate aminotransferase increased 1/28 (3.6%) 2 0/30 (0%) 2 0/32 (0%) 2 1/2 (50%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Blood bilirubin increased 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Blood chloride decreased 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Blood creatinine increased 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Blood immunoglobulin G decreased 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Chest X-ray abnormal 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Electrocardiogram QT prolonged 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Electrocardiogram ST segment depression 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Electrocardiogram T wave abnormal 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Heart rate irregular 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    N-terminal prohormone brain natriuretic peptide increased 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    White blood cells urine positive 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Metabolism and nutrition disorders
    Decreased appetite 5/28 (17.9%) 7 6/30 (20%) 7 6/32 (18.8%) 7 0/2 (0%) 7 1/3 (33.3%) 1 1/4 (25%) 1 1/8 (12.5%) 1 2/7 (28.6%) 4 3/8 (37.5%) 4
    Dehydration 7/28 (25%) 7 6/30 (20%) 15 3/32 (9.4%) 8 1/2 (50%) 1 1/3 (33.3%) 1 1/4 (25%) 1 1/8 (12.5%) 1 2/7 (28.6%) 3 0/8 (0%) 3
    Hypokalaemia 5/28 (17.9%) 7 3/30 (10%) 3 7/32 (21.9%) 8 1/2 (50%) 1 0/3 (0%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Hyponatraemia 2/28 (7.1%) 6 4/30 (13.3%) 7 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Hypomagnesaemia 2/28 (7.1%) 3 2/30 (6.7%) 3 1/32 (3.1%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hypophosphataemia 1/28 (3.6%) 1 1/30 (3.3%) 1 2/32 (6.3%) 4 0/2 (0%) 4 0/3 (0%) 4 0/4 (0%) 4 1/8 (12.5%) 4 0/7 (0%) 4 0/8 (0%) 4
    Hypocalcaemia 0/28 (0%) 0/30 (0%) 2/32 (6.3%) 2 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Hyperglycaemia 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 3 2/7 (28.6%) 2 2/8 (25%) 5
    Failure to thrive 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Fluid overload 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hyperkalaemia 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hypoalbuminaemia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 3/28 (10.7%) 4 4/30 (13.3%) 4 1/32 (3.1%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 2 0/8 (0%) 2
    Arthralgia 3/28 (10.7%) 4 3/30 (10%) 3 0/32 (0%) 3 0/2 (0%) 3 1/3 (33.3%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 1/8 (12.5%) 1
    Muscular weakness 2/28 (7.1%) 2 3/30 (10%) 4 0/32 (0%) 4 0/2 (0%) 4 0/3 (0%) 4 0/4 (0%) 4 0/8 (0%) 4 1/7 (14.3%) 1 1/8 (12.5%) 1
    Pain in extremity 1/28 (3.6%) 1 3/30 (10%) 4 0/32 (0%) 4 0/2 (0%) 4 1/3 (33.3%) 1 0/4 (0%) 1 2/8 (25%) 3 0/7 (0%) 3 0/8 (0%) 3
    Myalgia 0/28 (0%) 2/30 (6.7%) 3 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Muscle spasms 1/28 (3.6%) 1 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 2/8 (25%) 2
    Bone pain 1/28 (3.6%) 1 0/30 (0%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 2/8 (25%) 2 0/7 (0%) 2 1/8 (12.5%) 2
    Neck pain 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 2/8 (25%) 2 0/7 (0%) 2 0/8 (0%) 2
    Musculoskeletal chest pain 0/28 (0%) 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Musculoskeletal pain 0/28 (0%) 1/30 (3.3%) 1 1/32 (3.1%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Flank pain 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Nervous system disorders
    Headache 4/28 (14.3%) 5 7/30 (23.3%) 9 4/32 (12.5%) 4 0/2 (0%) 4 0/3 (0%) 4 1/4 (25%) 1 3/8 (37.5%) 16 2/7 (28.6%) 13 1/8 (12.5%) 1
    Dizziness 5/28 (17.9%) 5 4/30 (13.3%) 6 2/32 (6.3%) 2 2/2 (100%) 2 0/3 (0%) 2 1/4 (25%) 1 3/8 (37.5%) 4 1/7 (14.3%) 3 2/8 (25%) 4
    Dysphonia 1/28 (3.6%) 1/30 (3.3%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 2 0/4 (0%) 2 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Amnesia 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Aphasia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Brain oedema 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Dysarthria 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Dysgeusia 1/28 (3.6%) 1 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Hypoaesthesia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Memory impairment 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Motor dysfunction 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Paraesthesia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Peripheral sensory neuropathy 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Post herpetic neuralgia 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Presyncope 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Psychiatric disorders
    Anxiety 2/28 (7.1%) 2 3/30 (10%) 3 3/32 (9.4%) 3 0/2 (0%) 3 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Insomnia 1/28 (3.6%) 2 3/30 (10%) 3 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 1/4 (25%) 1 2/8 (25%) 13 1/7 (14.3%) 8 2/8 (25%) 2
    Depression 1/28 (3.6%) 1 2/30 (6.7%) 3 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Confusional state 0/28 (0%) 2/30 (6.7%) 2 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 0/8 (0%) 1
    Delirium 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Delusion 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Disorientation 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hallucination, visual 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Irritability 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Nightmare 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Restlessness 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Renal and urinary disorders
    Proteinuria 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Pollakiuria 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Acute kidney injury 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Urine flow decreased 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Reproductive system and breast disorders
    Erectile dysfunction 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Breast pain 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 5/28 (17.9%) 8 8/30 (26.7%) 10 3/32 (9.4%) 3 2/2 (100%) 3 1/3 (33.3%) 3 1/4 (25%) 1 5/8 (62.5%) 8 2/7 (28.6%) 2 2/8 (25%) 2
    Cough 6/28 (21.4%) 7 6/30 (20%) 7 3/32 (9.4%) 3 0/2 (0%) 3 1/3 (33.3%) 1 1/4 (25%) 1 4/8 (50%) 5 0/7 (0%) 5 0/8 (0%) 5
    Oropharyngeal pain 3/28 (10.7%) 5 4/30 (13.3%) 4 0/32 (0%) 4 1/2 (50%) 1 0/3 (0%) 1 1/4 (25%) 1 2/8 (25%) 3 0/7 (0%) 3 2/8 (25%) 3
    Productive cough 1/28 (3.6%) 2 3/30 (10%) 4 1/32 (3.1%) 1 1/2 (50%) 1 1/3 (33.3%) 1 1/4 (25%) 2 0/8 (0%) 2 1/7 (14.3%) 1 1/8 (12.5%) 3
    Haemoptysis 0/28 (0%) 1/30 (3.3%) 1 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 1/8 (12.5%) 1
    Hiccups 0/28 (0%) 2/30 (6.7%) 2 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Wheezing 0/28 (0%) 2/30 (6.7%) 2 1/32 (3.1%) 1 2/2 (100%) 2 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Epistaxis 1/28 (3.6%) 1 0/30 (0%) 1 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Nasal congestion 1/28 (3.6%) 1 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Chronic obstructive pulmonary disease 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 1/2 (50%) 1 1/3 (33.3%) 1 1/4 (25%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hypoxia 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 1/4 (25%) 1 1/8 (12.5%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Pleural effusion 0/28 (0%) 0/30 (0%) 0/32 (0%) 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Pulmonary congestion 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 1/4 (25%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Rhonchi 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Dyspnoea exertional 1/28 (3.6%) 2 0/30 (0%) 2 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Pleuritic pain 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Pulmonary embolism 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 1/4 (25%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Respiratory failure 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Skin and subcutaneous tissue disorders
    Alopecia 1/28 (3.6%) 1 2/30 (6.7%) 2 3/32 (9.4%) 3 0/2 (0%) 3 1/3 (33.3%) 1 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Pruritus 1/28 (3.6%) 1 2/30 (6.7%) 3 1/32 (3.1%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Rash 0/28 (0%) 1/30 (3.3%) 2 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 2/7 (28.6%) 2 0/8 (0%) 2
    Erythema 0/28 (0%) 2/30 (6.7%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Infusion related reaction 0/28 (0%) 3/30 (10%) 3 2/32 (6.3%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Dry skin 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hyperhidrosis 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hyperkeratosis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 2
    Night sweats 0/28 (0%) 1/30 (3.3%) 1 1/32 (3.1%) 2 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Pain of skin 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Rash erythematous 1/28 (3.6%) 2 0/30 (0%) 2 0/32 (0%) 2 0/2 (0%) 2 0/3 (0%) 2 0/4 (0%) 2 0/8 (0%) 2 1/7 (14.3%) 1 0/8 (0%) 1
    Skin atrophy 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Swelling face 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 1/7 (14.3%) 1 0/8 (0%) 1
    Vascular disorders
    Hypotension 2/28 (7.1%) 3 5/30 (16.7%) 5 2/32 (6.3%) 3 1/2 (50%) 2 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 1/7 (14.3%) 1 1/8 (12.5%) 1
    Thrombophlebitis 0/28 (0%) 0/30 (0%) 2/32 (6.3%) 3 0/2 (0%) 3 0/3 (0%) 3 0/4 (0%) 3 0/8 (0%) 3 0/7 (0%) 3 0/8 (0%) 3
    Aortic aneurysm 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Axillary vein thrombosis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Flushing 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 1/2 (50%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Haematoma 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Hypertension 0/28 (0%) 1/30 (3.3%) 1 0/32 (0%) 1 0/2 (0%) 1 0/3 (0%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 1/8 (12.5%) 1
    Jugular vein thrombosis 0/28 (0%) 0/30 (0%) 1/32 (3.1%) 1 0/2 (0%) 1 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Peripheral artery thrombosis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1
    Peripheral coldness 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 1/4 (25%) 2 0/8 (0%) 2 0/7 (0%) 2 0/8 (0%) 2
    Phlebitis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1
    Thrombophlebitis superficial 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Thrombosis 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 0/3 (0%) 0/4 (0%) 1/8 (12.5%) 1 0/7 (0%) 1 0/8 (0%) 1
    Venous thrombosis limb 0/28 (0%) 0/30 (0%) 0/32 (0%) 0/2 (0%) 1/3 (33.3%) 1 0/4 (0%) 1 0/8 (0%) 1 0/7 (0%) 1 0/8 (0%) 1

    Limitations/Caveats

    Limitation of the trial is small numbers of subjects, since it is a Phase 2 clinical trial. Small sample size may have reduced the ability to observe statistically significant treatment effects on secondary myelopreservation measures (i.e. occurrence of FN AEs, infections and antibiotics usage).

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Clinical Trial Info.
    Organization G1 Therapeutics, Inc.
    Phone 919-213-9835
    Email clinicalinfo@g1therapeutics.com
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT02514447
    Other Study ID Numbers:
    • G1T28-03
    • 2016-004611-13
    First Posted:
    Aug 3, 2015
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    May 1, 2022