Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

• Sponsor: G1 Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02978716
• Collaborator: (none)
• Enrollment: 102
• Locations: 54
• Arms: 3
• Actual Duration (Months): 36.8
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for participants with metastatic triple negative breast cancer.

The study was an open-label and 102 participants were randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups:

• Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=34)

• Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=33)

• Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=35)

The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Condition or Disease	Intervention/Treatment	Phase
Triple-Negative Breast Neoplasms; Breast Neoplasm; Breast Cancer; Triple-Negative Breast Cancer	Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin	Phase 2

Detailed Description

The posted results represent the final results of Study G1T28-04, a Phase 2 study of the safety, efficacy and pharmacokinetics of trilaciclib (G1T28) in patients with locally recurrent/metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy.

The final myelopreservation efficacy results are reported from database lock 1 ([DBL1], data cut-off [DCO] date of 30 July 2018). Final anti-tumor efficacy (ORR, PFS), and final summary exposure and safety data are reported from database lock 2 ([DBL2], DCO 28 June 2019) which occurred to support filing of the trilaciclib New Drug Application (NDA). Final overall survival (OS) data are reported from the final database lock which occurred on 17 July 2020 (with a last patient last visit date of 28 February 2020).

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy
• Actual Study Start Date: Feb 2, 2017
• Actual Primary Completion Date: Jun 28, 2019
• Actual Study Completion Date: Feb 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Gemcitabine/Carboplatin (Days 1 and 8) Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin
Experimental: Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8) Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.	Drug: Trilaciclib; G1T28; Other Names: G1T28 CDK 4/6 Inhibitor ; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin
Experimental: Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9) Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.	Drug: Trilaciclib; G1T28; Other Names: G1T28 CDK 4/6 Inhibitor ; Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin

Outcome Measures

Primary Outcome Measures

1. Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1 [From randomization to the end of Cycle 1 (Each cycle= 21 days)]

   DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (<) 0.5 × 10^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (>=) 0.5 × 10^9/L that met the following: (1) occurred after the ANC value of < 0.5 × 10^9 cells/L and (2) no other ANC values < 0.5 × 10^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated.

2. Number of Participants With Severe (Grade 4) Neutropenia (SN) [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

   Number of participants with Grade 4 SN was a binary variable. If a participants had at least 1 ANC value < 0.5 ×10^9/L during the treatment period, the participants was assigned as "yes" to the occurrence of SN. Otherwise, it was "no".

Secondary Outcome Measures

1. Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days]

   BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing.

2. Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator [From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days]

   DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method.

3. Overall Survival (OS) [From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days]

   Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method.

4. Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator [From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days]

   PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method.

5. Relative Dose Intensity of Gemcitabine and Carboplatin [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 871 days]

   Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 * [Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)]); for carboplatin (100 * [Dose intensity (AUC/week)/ (4/3) (AUC/week)]) and for trilaciclib (100 * [Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)] for Group 2 and 100 * [Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)] for Group 3).

6. Duration of 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 871 days]

   Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.

7. Number of Cycles Participants Received Treatment in Each Treatment Arm [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 871 days]

   Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.

8. Cumulative Dose of Gemcitabine [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 871 days]

   Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]).

9. Cumulative Dose of Carboplatin [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 871 days]

   Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).

10. Maximum Observed Plasma Concentration (Cmax) of Trilaciclib [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    The observed peak plasma concentration was determined from the plasma concentration-versus time data.

11. Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations.

12. Terminal Elimination Half-Life (t1/2) of Trilaciclib [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg*h/L).

13. Maximum Observed Plasma Concentration (Cmax) of Gemcitabine [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    The observed peak plasma concentration was determined from the plasma concentration-versus time data.

14. Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    AUC0-t was calculated with the linear/log-trapezoidal method.

15. Terminal Elimination Half-Life (t1/2) of Free Carboplatin [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.

16. Clearance (CL) of of Free Carboplatin [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase.

17. Volume of Distribution at Steady State (Vss) of Free Carboplatin [Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)]

    Vss was the volume of distribution at steady state of free carboplatin was reported.

18. Number of Participants With Grade 3 and 4 Hematologic Toxicities [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant.

19. Number of Participants With Grade 3 or 4 Thrombocytopenia [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as "Yes" to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was "No". If a participant did not have an event, the value of 0 was assigned to that participant.

20. Major Adverse Hematologic Event (MAHE) Rate [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration > 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week.

21. Number of Participants With Febrile Neutropenia (FN) [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    The criterion for identifying FN was if the PT was "FEBRILE NEUTROPENIA" the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.

22. Number of Participants With Infection SAEs [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    Number of participants with infection SAEs during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion for identifying the proper infection SAE records was as follows: If the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.

23. Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35) [From Day 35 through the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 508 days]

    Each RBC transfusion with a unique start date on/after 5 weeks on study during the treatment period was defined as a separate event. Occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

24. Number of Participants With Platelet Transfusions [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    Each platelet transfusion with a unique start date during the treatment period was defined as a separate event. The occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if the total number of events >=1 was observed and No for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

25. Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    The criterion for selecting proper records is as follows: If the chemical subgroup from the World Health Organization-Drug Dictionary (WHO-DD) takes value "COLONY STIMULATING FACTOR," the medication was classified as G-CSF. The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

26. Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (i.e., TEXT4 for CODE4) takes value "OTHER ANTIANEMIC PREPARATIONS", the medication was classified as ESAs.

27. Number of Participants With Intravenous Antibiotics Use [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    The criteria for identifying an IV antibiotic administration event was (1) if the Therapeutic subgroup from WHO-DD version takes value "ANTIBACTERIALS FOR SYSTEMIC USE", and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB". The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.

28. All-cause Dose Reductions, Event Rate (Per Cycle) [During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days]

    Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles.

29. Dose Modifications: Number of Participants With Cycle Delays [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 871 days]

    Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment.

30. Dose Modifications - Number of Participants With Skipped Doses [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 871 days]

    Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays).

31. Dose Modifications: Number of Participants With Any Dose Interruptions [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 871 days]

    Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

32. Dose Modifications - Number of Participants With Dose Reductions [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 871 days]

    Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle.

Other Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [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 1116 days]

   An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer

• Available TNBC diagnostic tumor tissue (archived tissue allowed)

• Evaluable disease

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

• Adequate organ function

• Predicted life expectancy of 3 or more months

Exclusion Criteria:

• More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.

• CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.

• Investigational drug within 30 days of first trilaciclib (G1T28) dose

• Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose

• Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose

• Prior hematopoietic stem cell or bone marrow transplantation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85704
2	Disney Family Cancer Center	Burbank	California	United States	91505
3	Sharp Clinical Oncology	San Diego	California	United States	92123
4	Innovative Clinical Research Institute	Whittier	California	United States	90603
5	Memorial UC Health	Colorado Springs	Colorado	United States	80909
6	Rocky Mountain Cancer Centers	Lakewood	Colorado	United States	80228
7	Florida Cancer Specialists	Fort Myers	Florida	United States	33916
8	Florida Cancer Research Institute, LLC.	Plantation	Florida	United States	33324
9	Florida Cancer Specialists - North (FCS North)	Saint Petersburg	Florida	United States	33705
10	Moffitt Cancer Center	Tampa	Florida	United States	33612
11	Florida Cancer Specialists - East (FCS East)	West Palm Beach	Florida	United States	33401
12	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
13	Illinois Cancer Specialists	Arlington Heights	Illinois	United States	60005
14	Community Health Network	Indianapolis	Indiana	United States	46250
15	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201-1544
16	The University of Maryland St. Joseph Medical Center	Towson	Maryland	United States	21204
17	Saint Luke's Cancer Institute	Kansas City	Missouri	United States	64113
18	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89128
19	Levine Cancer Center	Charlotte	North Carolina	United States	28204
20	Forsyth Memorial Hospital, Novant Health Oncology Specialists	Winston-Salem	North Carolina	United States	27103
21	Tennessee Oncology	Chattanooga	Tennessee	United States	37404
22	Tennessee Oncology	Nashville	Tennessee	United States	37203
23	Texas Oncology-Dallas Presbyterian Hospital	Austin	Texas	United States	75231
24	Texas Oncology, P.A.	Austin	Texas	United States	78745
25	Texas Oncology, P.A.	Bedford	Texas	United States	76022
26	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
27	Texas Oncology-El Paso Cancer Treatment Center Grandview	El Paso	Texas	United States	79902
28	The Center for Cancer and Blood Disorders	Fort Worth	Texas	United States	76104
29	Texas Oncology-San Antonio Northeast	San Antonio	Texas	United States	78217
30	Tyler Hematology-Oncology, PA	Tyler	Texas	United States	75701
31	Texas Oncology, P.A.	Tyler	Texas	United States	75702
32	University of Virginia	Charlottesville	Virginia	United States	22908
33	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
34	Virginia Oncology Associates	Virginia Beach	Virginia	United States	23456
35	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
36	Antwerp University Hospital (UZA)	Edegem		Belgium	10 2650
37	University Multiprofile Hospital for Active Treatment	Sofia		Bulgaria	1000
38	MHAT for Womens Health - Nadezhda OOD	Sofia		Bulgaria	1330
39	Special Hospital For Active Treatment In Oncology	Sofia		Bulgaria	1756
40	Multiprofile Hospital for Active Treatment	Varna		Bulgaria	9000
41	University Hospital Centre Osijek	Osijek		Croatia	31000
42	General Hospital Varaždin	Varazdin		Croatia	42000
43	University Hospital Centre "Sestre milosrdnice"	Zagreb		Croatia	10000
44	University Hospital Centre Zagreb	Zagreb		Croatia	10000
45	Clinical Hospital Dr. Trifun Panovski	Bitola		North Macedonia	7000
46	University Clinic of Radiotherapy and Oncology	Skopje		North Macedonia	1000
47	Special Hospital for Internal Diseases , Oncomed	Belgrade		Serbia	11000
48	Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic	Belgrade		Serbia	11070
49	Center for Oncology and Radiotherapy, Clinical Centre	Kragujevac		Serbia	34000
50	Clinical Centre Nis, Clinic of Oncology	Nis		Serbia	18000
51	Oncology Institute of Vojvodina, Clinic for Internal Oncology	Sremska Kamenica		Serbia	21204
52	Mammacentrum, Sv.Agáty	Banská Bystrica		Slovakia	974 01
53	Cancer Institute VOU, Rastislavova	Košice		Slovakia	040 01
54	University Medical Centre Maribor	Maribor		Slovenia	2000

Sponsors and Collaborators

• G1 Therapeutics, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Aug 31, 2017
• Statistical Analysis Plan - Sep 28, 2018

More Information

Publications

• Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Xiao J, Sorrentino J, Horton J, O'Shaughnessy J. Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study. Clin Cancer Res. 2022 Feb 15;28(4):629-636. doi: 10.1158/1078-0432.CCR-21-2272.
• Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnović Ž, Vasev N, Ma L, Richards DA, Wilks ST, Milenković D, Yang Z, Antal JM, Morris SR, O'Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019 Nov;20(11):1587-1601. doi: 10.1016/S1470-2045(19)30616-3. Epub 2019 Sep 28.

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02978716
• Other Study ID Numbers: G1T28-04; 2016-004466-26
• First Posted: Dec 1, 2016
• Last Update Posted: Mar 23, 2022
• Last Verified: Feb 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.: Breast Cancer; CDK 4/6 Inhibitor; Triple Negative Breast Cancer; Metastatic
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasms; Triple Negative Breast Neoplasms; Gemcitabine; Carboplatin

Study Results

Participant Flow

Recruitment Details	This study was conducted at 34 sites in the United States (US), Belgium, Bulgaria, Croatia, Republic of Macedonia, and Serbia from 02 February 2017 (first participant enrolled) to 28 February 2020 (last participant last visit).
Pre-assignment Detail	Participants were screened within 28 days before the first dose of the treatment. Informed consent was obtained up to 28 days prior to first study drug administration. For tumor assessment, all sites of disease were assessed radiologically at screening. A total of 102 participants were randomized in this study.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Period Title: Overall Study
STARTED	34	33	35
ITT Population	34	33	35
Safety Analysis Set	30	33	35
Treated	30	33	35
COMPLETED	0	0	0
NOT COMPLETED	34	33	35

Baseline Characteristics

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)	Total
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Total of all reporting groups
Overall Participants	34	33	35	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (13.6)	56 (12.1)	58 (9.5)	56 (11.8)
Sex: Female, Male (Count of Participants)
Female	34 100%	32 97%	35 100%	101 99%
Male	0 0%	1 3%	0 0%	1 1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.9%	5 15.2%	2 5.7%	9 8.8%
Not Hispanic or Latino	32 94.1%	28 84.8%	33 94.3%	93 91.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 6.1%	4 11.4%	6 5.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	5 14.7%	7 21.2%	2 5.7%	14 13.7%
White	28 82.4%	22 66.7%	28 80%	78 76.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.9%	2 6.1%	1 2.9%	4 3.9%

Outcome Measures

1. Primary Outcome

Title	Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1
Description	DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (<) 0.5 × 10^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (>=) 0.5 × 10^9/L that met the following: (1) occurred after the ANC value of < 0.5 × 10^9 cells/L and (2) no other ANC values < 0.5 × 10^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated.
Time Frame	From randomization to the end of Cycle 1 (Each cycle= 21 days)

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Mean (Standard Deviation) [days]	1 (2.2)	2 (3.5)	1 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	Duration of SN in Cycle 1 in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	A Hochberg-based gatekeeping procedure was used to control the global family-wise error rate across the multiple null hypotheses in the strong sense at a 1-sided 0.025 level.
	Method	Analysis of covariance (ANCOVA)
	Comments
Method of Estimation	Estimation Parameter	Mean difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.58
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	Duration of SN in Cycle 1 in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3364
	Comments	2-sided p-value was calculated using a ANCOVA with study baseline ANC value as covariate, stratification factors of lines of systemic therapy, liver involvement and treatment as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.6 to 2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.71
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Severe (Grade 4) Neutropenia (SN)
Description	Number of participants with Grade 4 SN was a binary variable. If a participants had at least 1 ANC value < 0.5 ×10^9/L during the treatment period, the participants was assigned as "yes" to the occurrence of SN. Otherwise, it was "no".
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Grade 4 neutropenia: Yes	9 26.5%	12 36.4%	8 22.9%
Grade 4 neutropenia: No	25 73.5%	21 63.6%	27 77.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	Number of participants with SN in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
	Method	Modified Poisson method
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.776
	Confidence Interval	(2-Sided) 95%; 0.386 to 1.559
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2762
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	Number of participants with SN in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9154
	Comments	The p-value was calculated using modified Poisson method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors and baseline ANC as a covariate.
	Method	Modified Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.961
	Confidence Interval	(2-Sided) 95%; 0.457 to 2.019
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3640
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Description	BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing.
Time Frame	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

Outcome Measure Data

Analysis Population Description

The response-evaluable (RE) analysis set included all participants who were in the modified intent-to-treat (mITT) analysis set, had measurable disease (target lesions [TLs]) at the baseline tumor assessment, and had (1) at least 1 post-baseline tumor assessment, (2) clinical progression (as noted by the investigator) before their first post-baseline tumor scan, or (3) died due to disease progression before their first post-baseline tumor scan.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	24	30	31
Complete response (CR)	0 0%	0 0%	0 0%
Partial response (PR)	7 20.6%	15 45.5%	11 31.4%
Stable disease (SD)	11 32.4%	9 27.3%	15 42.9%
Progressive disease (PD)	6 17.6%	5 15.2%	3 8.6%
Not evaluable (NE)	0 0%	0 0%	1 2.9%
Missing	0 0%	1 3%	1 2.9%

4. Secondary Outcome

Title	Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator
Description	DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method.
Time Frame	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

Outcome Measure Data

Analysis Population Description

The RE analysis set included all participants who were in the mITT analysis set, had measurable disease TLs at the baseline tumor assessment, and had (1) at least 1 post-baseline tumor assessment, (2) clinical progression (as noted by the investigator) before their first post-baseline tumor scan, or (3) died due to disease progression before their first post-baseline tumor scan. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	7	15	11
Median (95% Confidence Interval) [months]	7.8	11.5	9.6

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method.
Time Frame	From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Median (95% Confidence Interval) [months]	12.6	NA	17.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	Overall survival in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	P-value was calculated using the stratified log-rank test to account for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Adjusted hazard ratio (HR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.125
	Estimation Comments	Cox regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	Overall survival in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments	P-value was calculated using the stratified log-rank test to account for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
	Method	stratified log-rank test
	Comments
Method of Estimation	Estimation Parameter	Adjusted HR
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.111
	Estimation Comments	Cox regression model.

6. Secondary Outcome

Title	Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator
Description	PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method.
Time Frame	From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Median (95% Confidence Interval) [months]	5.7	9.4	7.3

7. Secondary Outcome

Title	Relative Dose Intensity of Gemcitabine and Carboplatin
Description	Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 * [Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)]); for carboplatin (100 * [Dose intensity (AUC/week)/ (4/3) (AUC/week)]) and for trilaciclib (100 * [Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)] for Group 2 and 100 * [Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)] for Group 3).
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Carboplatin	77.5 (19.20)	79.1 (15.88)	81.7 (16.09)
Gemcitabine	79.1 (18.29)	80.8 (12.51)	81.0 (14.49)

8. Secondary Outcome

Title	Duration of Exposure
Description	Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Median (Full Range) [days]	101	161	168

9. Secondary Outcome

Title	Number of Cycles Participants Received Treatment in Each Treatment Arm
Description	Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Mean (Standard Deviation) [number of cycles]	6 (5.0)	9 (6.6)	8 (4.8)

10. Secondary Outcome

Title	Cumulative Dose of Gemcitabine
Description	Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]).
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Mean (Standard Deviation) [mg/m^2]	10694.3 (9029.11)	14680.9 (11557.90)	13277.2 (8722.51)

11. Secondary Outcome

Title	Cumulative Dose of Carboplatin
Description	Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Mean (Standard Deviation) [AUC (mg/mL/min)]	20.3 (16.47)	27.8 (21.21)	26.0 (16.33)

12. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Trilaciclib
Description	The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	0	6	7
Mean (Standard Deviation) [ng/mL]	2280 (1790)	1630 (423)

13. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib
Description	AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	0	6	7
Mean (Standard Deviation) [hour* nanogram per milliliter (h*ng/mL)]	3610 (1870)	3800 (910)

14. Secondary Outcome

Title	Terminal Elimination Half-Life (t1/2) of Trilaciclib
Description	t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg*h/L).
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Since, no participant received Trilaciclib in Group 1, data was not assessed and reported.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	0	5	6
Median (Full Range) [hours]	5.27	5.31

15. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
Description	The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	1	5	5
Mean (Standard Deviation) [microgram per milliliter (mcg/mL)]	NA (NA)	18.0 (4.04)	23.8 (25.9)

16. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine
Description	AUC0-t was calculated with the linear/log-trapezoidal method.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	1	5	5
Mean (Standard Deviation) [hour*microgram per milliliter (h*mcg/mL)]	NA	20.4 (11.6)	15.4 (7.11)

17. Secondary Outcome

Title	Terminal Elimination Half-Life (t1/2) of Free Carboplatin
Description	t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	1	5	5
Median (Full Range) [hours]	5.23	2.49	1.79

18. Secondary Outcome

Title	Clearance (CL) of of Free Carboplatin
Description	Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	1	3	5
Mean (Standard Deviation) [Liter/hour (L/h)]	6.65	14.0 (2.80)	13.7 (4.48)

19. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of Free Carboplatin
Description	Vss was the volume of distribution at steady state of free carboplatin was reported.
Time Frame	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Outcome Measure Data

Analysis Population Description

The PK analysis set included all dosed participants with evaluable PK data. Here, "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	1	5	5
Mean (Standard Deviation) [Liter]	44.4	35.0 (12.0)	34.0 (8.99)

20. Secondary Outcome

Title	Number of Participants With Grade 3 and 4 Hematologic Toxicities
Description	Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with Grade 3 and 4 hematologic toxicities: Yes	25 73.5%	30 90.9%	27 77.1%
Participants with Grade 3 and 4 hematologic toxicities: No	9 26.5%	3 9.1%	8 22.9%

21. Secondary Outcome

Title	Number of Participants With Grade 3 or 4 Thrombocytopenia
Description	Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as "Yes" to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was "No". If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Count of Participants [Participants]	21 61.8%	12 36.4%	19 54.3%

22. Secondary Outcome

Title	Major Adverse Hematologic Event (MAHE) Rate
Description	MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration > 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Number [event rate per week]	0.153	0.108	0.080

23. Secondary Outcome

Title	Number of Participants With Febrile Neutropenia (FN)
Description	The criterion for identifying FN was if the PT was "FEBRILE NEUTROPENIA" the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Count of Participants [Participants]	1 2.9%	1 3%	0 0%

24. Secondary Outcome

Title	Number of Participants With Infection SAEs
Description	Number of participants with infection SAEs during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion for identifying the proper infection SAE records was as follows: If the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with Infection SAEs: Yes	2 5.9%	0 0%	0 0%
Participants with Infection SAEs: No	32 94.1%	33 100%	35 100%

25. Secondary Outcome

Title	Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)
Description	Each RBC transfusion with a unique start date on/after 5 weeks on study during the treatment period was defined as a separate event. Occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame	From Day 35 through the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 508 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with RBC transfusions on/after Week 5: Yes	12 35.3%	11 33.3%	8 22.9%
Participants with RBC transfusions on/after Week 5: No	22 64.7%	22 66.7%	27 77.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	RBC Transfusions in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
	Method	modified Poisson regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted HR
	Estimated Value	0.493
	Confidence Interval	(2-Sided) 95%; 0.226 to 1.073
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1957
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	RBC Transfusions in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7272
	Comments	P-value was calculated using modified Poisson method adjusting for duration of treatment in days accounting for number of prior lines of therapy (0 versus 1 - 2); liver involvement as the stratification factors and baseline hemoglobin as a covariate.
	Method	Modified Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.885
	Confidence Interval	(2-Sided) 95%; 0.447 to 1.754
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3089
	Estimation Comments

26. Secondary Outcome

Title	Number of Participants With Platelet Transfusions
Description	Each platelet transfusion with a unique start date during the treatment period was defined as a separate event. The occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if the total number of events >=1 was observed and No for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with platelet transfusion: Yes	4 11.8%	3 9.1%	6 17.1%
Participants with platelet transfusion: No	30 88.2%	30 90.9%	29 82.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	Platelet Transfusions in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
	Method	modified Poisson regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.988
	Confidence Interval	(2-Sided) 95%; 0.294 to 3.317
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6105
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	Platelet Transfusions in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4078
	Comments	P-value: calculated using modified Poisson method adjusting for duration of treatment in days accounting for number of prior lines of therapy (0 versus 1 - 2); liver involvement as stratification factors and baseline platelet count as a covariate.
	Method	Modified Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.527
	Confidence Interval	(2-Sided) 95%; 0.116 to 2.399
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4077
	Estimation Comments

27. Secondary Outcome

Title	Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration
Description	The criterion for selecting proper records is as follows: If the chemical subgroup from the World Health Organization-Drug Dictionary (WHO-DD) takes value "COLONY STIMULATING FACTOR," the medication was classified as G-CSF. The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with G-CSF Administration: Yes	16 47.1%	21 63.6%	14 40%
Participants with G-CSF Administration: No	18 52.9%	12 36.4%	21 60%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	G-CSF Administration in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	A 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global familywise error rate across the multiple null hypotheses.
	Method	modified Poisson regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.645
	Confidence Interval	(2-Sided) 95%; 0.362 to 1.150
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1902
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	G-CSF Administration in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7835
	Comments	P-value was calculated using modified Poisson method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors and baseline ANC as a covariate.
	Method	Modified Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.936
	Confidence Interval	(2-Sided) 95%; 0.583 to 1.502
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2260
	Estimation Comments

28. Secondary Outcome

Title	Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration
Description	The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (i.e., TEXT4 for CODE4) takes value "OTHER ANTIANEMIC PREPARATIONS", the medication was classified as ESAs.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with ESA Administration: Yes	4 11.8%	2 6.1%	3 8.6%
Participants with ESA Administration: No	30 88.2%	31 93.9%	32 91.4%

29. Secondary Outcome

Title	Number of Participants With Intravenous Antibiotics Use
Description	The criteria for identifying an IV antibiotic administration event was (1) if the Therapeutic subgroup from WHO-DD version takes value "ANTIBACTERIALS FOR SYSTEMIC USE", and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB". The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Day 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Participants with Intravenous Antibiotics Use: Yes	6 17.6%	5 15.2%	0 0%
Participants with Intravenous Antibiotics Use: No	28 82.4%	28 84.8%	35 100%

30. Secondary Outcome

Title	All-cause Dose Reductions, Event Rate (Per Cycle)
Description	Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles.
Time Frame	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Outcome Measure Data

Analysis Population Description

The ITT analysis set included all randomized participants.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	34	33	35
Number [event rate per cycle]	0.141	0.118	0.133

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Comments	All-cause Dose Reductions in Group 3 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7048
	Comments	The 1-sided p-value was calculated using Hochberg-based gatekeeping procedure to control the global family wise error rate across the multiple null hypotheses.
	Method	negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.991
	Confidence Interval	(2-Sided) 95%; 0.475 to 2.067
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3718
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1: Gemcitabine/Carboplatin (Days 1 and 8), Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)
	Comments	All-cause Dose Reductions in Group 2 vs Group 1.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5541
	Comments	P-value was calculated using negative binomial method adjusting for number of cycles, accounting for the number of prior lines of therapy (0 versus 1 - 2) and liver involvement as the stratification factors.
	Method	negative binomial regression
	Comments
Method of Estimation	Estimation Parameter	Adjusted rate ratio
	Estimated Value	0.820
	Confidence Interval	(2-Sided) 95%; 0.426 to 1.580
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2744
	Estimation Comments

31. Secondary Outcome

Title	Dose Modifications: Number of Participants With Cycle Delays
Description	Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment.
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Count of Participants [Participants]	17 50%	19 57.6%	22 62.9%

32. Secondary Outcome

Title	Dose Modifications - Number of Participants With Skipped Doses
Description	Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays).
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Count of Participants [Participants]	15 44.1%	20 60.6%	13 37.1%

33. Secondary Outcome

Title	Dose Modifications: Number of Participants With Any Dose Interruptions
Description	Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Trilaciclib	NA NaN	3 9.1%	5 14.3%
Carboplatin	1 2.9%	1 3%	0 0%
Gemcitabine	2 5.9%	4 12.1%	0 0%

34. Secondary Outcome

Title	Dose Modifications - Number of Participants With Dose Reductions
Description	Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle.
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 871 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Carboplatin	10 29.4%	13 39.4%	15 42.9%
Gemcitabine	13 38.2%	20 60.6%	17 48.6%

35. Other Pre-specified Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs.
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 1116 days

Outcome Measure Data

Analysis Population Description

The safety analysis set included all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)	Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).	Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.	Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
Measure Participants	30	33	35
Participants with any TEAEs	30 88.2%	33 100%	34 97.1%
Participants with any Serious TEAEs	10 29.4%	11 33.3%	4 11.4%

Adverse Events

Time Frame	From date of randomization up to 1121 days
Adverse Event Reporting Description	Safety evaluations were conducted at baseline and throughout the study. Safety surveillance reporting of AEs and SAEs commenced at the time of informed consent and continued through 30 days after the last dose of study drug (safety follow-up phone call). The safety analysis set included all enrolled participants who received at least 1 dose of study drug.
Arm/Group Title	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)		Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8)		Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
Arm/Group Description	Participants received IV infusion of standard GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) on Days 1 and 8 of 21-day cycles. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).		Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.		Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day cycles. Trilaciclib was administered prior to chemotherapy.
All Cause Mortality
	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)		Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8)		Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/30 (83.3%)		13/33 (39.4%)		20/35 (57.1%)
Serious Adverse Events
	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)		Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8)		Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/30 (33.3%)		11/33 (33.3%)		4/35 (11.4%)
Blood and lymphatic system disorders
Febrile neutropenia	1/30 (3.3%)	1	1/33 (3%)	1	0/35 (0%)	0
Normochromic normocytic anaemia	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Thrombocytopenia	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Cardiac disorders
Acute left ventricular failure	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Acute myocardial infarction	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Cardiac arrest	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Pericardial effusion	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Right ventricular failure	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Ascites	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Enteritis	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Faecaloma	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Oesophageal stenosis	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Varices oesophageal	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
General disorders
Non-cardiac chest pain	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	2
Pain	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Infections and infestations
Cellulitis	2/30 (6.7%)	2	0/33 (0%)	0	0/35 (0%)	0
Bacteraemia	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Lung infection	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Septic shock	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Injury, poisoning and procedural complications
Lumbar vertebral fracture	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Subdural haematoma	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Investigations
Platelet count decreased	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Hypercalcaemia	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Musculoskeletal and connective tissue disorders
Myositis	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Nervous system disorders
Syncope	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Psychiatric disorders
Suicidal ideation	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Renal and urinary disorders
Haematuria	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Urinary tract obstruction	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/30 (3.3%)	2	1/33 (3%)	1	0/35 (0%)	0
Pleural effusion	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Pulmonary embolism	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Acute respiratory failure	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Obstructive airways disorder	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Pleuritic pain	0/30 (0%)	0	0/33 (0%)	0	1/35 (2.9%)	1
Vascular disorders
Embolism	0/30 (0%)	0	1/33 (3%)	1	0/35 (0%)	0
Hypertension	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Hypotension	1/30 (3.3%)	1	0/33 (0%)	0	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1: Gemcitabine/Carboplatin (Days 1 and 8)		Group 2: Trilaciclib (G1T28)+ Gemcitabine/Carboplatin (Days 1 and 8)		Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/30 (100%)		33/33 (100%)		34/35 (97.1%)
Blood and lymphatic system disorders
Anaemia	22/30 (73.3%)	61	16/33 (48.5%)	46	15/35 (42.9%)	35
Neutropenia	13/30 (43.3%)	49	15/33 (45.5%)	79	12/35 (34.3%)	31
Thrombocytopenia	13/30 (43.3%)	68	13/33 (39.4%)	55	11/35 (31.4%)	55
Leukopenia	5/30 (16.7%)	9	3/33 (9.1%)	12	1/35 (2.9%)	3
Ear and labyrinth disorders
Tinnitus	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Eye disorders
Lacrimation increased	1/30 (3.3%)	1	0/33 (0%)	0	2/35 (5.7%)	2
Gastrointestinal disorders
Nausea	7/30 (23.3%)	8	14/33 (42.4%)	19	17/35 (48.6%)	31
Vomiting	8/30 (26.7%)	9	8/33 (24.2%)	23	11/35 (31.4%)	18
Constipation	5/30 (16.7%)	6	9/33 (27.3%)	16	9/35 (25.7%)	11
Diarrhoea	4/30 (13.3%)	4	9/33 (27.3%)	15	5/35 (14.3%)	6
Gastrooesophageal reflux disease	3/30 (10%)	3	5/33 (15.2%)	5	1/35 (2.9%)	1
Abdominal pain	1/30 (3.3%)	1	4/33 (12.1%)	6	2/35 (5.7%)	3
Abdominal pain upper	1/30 (3.3%)	1	3/33 (9.1%)	3	3/35 (8.6%)	3
Stomatitis	2/30 (6.7%)	5	1/33 (3%)	1	2/35 (5.7%)	3
Abdominal distension	0/30 (0%)	0	3/33 (9.1%)	3	1/35 (2.9%)	1
Flatulence	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
General disorders
Fatigue	11/30 (36.7%)	17	14/33 (42.4%)	22	16/35 (45.7%)	35
Oedema peripheral	4/30 (13.3%)	5	4/33 (12.1%)	7	4/35 (11.4%)	8
Pyrexia	3/30 (10%)	3	6/33 (18.2%)	8	2/35 (5.7%)	2
Pain	5/30 (16.7%)	7	2/33 (6.1%)	2	3/35 (8.6%)	3
Chills	0/30 (0%)	0	6/33 (18.2%)	7	1/35 (2.9%)	1
Influenza like illness	0/30 (0%)	0	0/33 (0%)	0	4/35 (11.4%)	5
Catheter site pain	1/30 (3.3%)	1	0/33 (0%)	0	2/35 (5.7%)	2
Chest pain	1/30 (3.3%)	1	0/33 (0%)	0	2/35 (5.7%)	2
Chest discomfort	0/30 (0%)	0	0/33 (0%)	0	2/35 (5.7%)	4
Infusion site pain	0/30 (0%)	0	0/33 (0%)	0	2/35 (5.7%)	2
Mucosal inflammation	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Infections and infestations
Urinary tract infection	5/30 (16.7%)	5	4/33 (12.1%)	4	3/35 (8.6%)	4
Pneumonia	1/30 (3.3%)	1	3/33 (9.1%)	3	0/35 (0%)	0
Sinusitis	1/30 (3.3%)	1	1/33 (3%)	1	2/35 (5.7%)	3
Upper respiratory tract infection	1/30 (3.3%)	1	2/33 (6.1%)	3	0/35 (0%)	0
Nasopharyngitis	2/30 (6.7%)	2	0/33 (0%)	0	0/35 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	1/30 (3.3%)	1	7/33 (21.2%)	35	4/35 (11.4%)	6
Investigations
Neutrophil count decreased	8/30 (26.7%)	20	12/33 (36.4%)	50	11/35 (31.4%)	30
Platelet count decreased	8/30 (26.7%)	38	8/33 (24.2%)	13	12/35 (34.3%)	44
Alanine aminotransferase increased	3/30 (10%)	5	4/33 (12.1%)	6	4/35 (11.4%)	4
Aspartate aminotransferase increased	3/30 (10%)	6	4/33 (12.1%)	5	4/35 (11.4%)	7
White blood cell count decreased	2/30 (6.7%)	7	4/33 (12.1%)	7	2/35 (5.7%)	5
Blood alkaline phosphatase increased	2/30 (6.7%)	2	2/33 (6.1%)	2	0/35 (0%)	0
Weight decreased	0/30 (0%)	0	2/33 (6.1%)	3	1/35 (2.9%)	1
Haemoglobin decreased	0/30 (0%)	0	2/33 (6.1%)	2	0/35 (0%)	0
Weight increased	0/30 (0%)	0	0/33 (0%)	0	2/35 (5.7%)	2
Metabolism and nutrition disorders
Hypokalaemia	3/30 (10%)	3	4/33 (12.1%)	5	5/35 (14.3%)	5
Decreased appetite	2/30 (6.7%)	2	5/33 (15.2%)	6	4/35 (11.4%)	7
Hypomagnesaemia	2/30 (6.7%)	2	1/33 (3%)	1	2/35 (5.7%)	2
Hyponatraemia	1/30 (3.3%)	3	2/33 (6.1%)	2	2/35 (5.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	3/30 (10%)	3	7/33 (21.2%)	15	3/35 (8.6%)	5
Arthralgia	3/30 (10%)	4	6/33 (18.2%)	7	3/35 (8.6%)	4
Pain in extremity	2/30 (6.7%)	3	4/33 (12.1%)	6	3/35 (8.6%)	4
Bone pain	4/30 (13.3%)	5	2/33 (6.1%)	2	2/35 (5.7%)	3
Myalgia	5/30 (16.7%)	5	2/33 (6.1%)	2	1/35 (2.9%)	1
Musculoskeletal chest pain	1/30 (3.3%)	1	2/33 (6.1%)	3	3/35 (8.6%)	3
Musculoskeletal pain	1/30 (3.3%)	1	1/33 (3%)	1	4/35 (11.4%)	6
Flank pain	0/30 (0%)	0	3/33 (9.1%)	6	1/35 (2.9%)	2
Muscular weakness	0/30 (0%)	0	3/33 (9.1%)	3	0/35 (0%)	0
Hypophosphataemia	0/30 (0%)	0	3/33 (9.1%)	4	3/35 (8.6%)	7
Dehydration	4/30 (13.3%)	4	0/33 (0%)	0	1/35 (2.9%)	1
Hypoalbuminaemia	1/30 (3.3%)	1	1/33 (3%)	2	2/35 (5.7%)	2
Hypocalcaemia	1/30 (3.3%)	3	2/33 (6.1%)	2	0/35 (0%)	0
Hyperlipidaemia	2/30 (6.7%)	2	0/33 (0%)	0	0/35 (0%)	0
Nervous system disorders
Headache	6/30 (20%)	9	9/33 (27.3%)	11	14/35 (40%)	22
Dizziness	6/30 (20%)	8	4/33 (12.1%)	7	6/35 (17.1%)	11
Dysgeusia	0/30 (0%)	0	5/33 (15.2%)	5	1/35 (2.9%)	1
Cognitive disorders	1/30 (3.3%)	1	2/33 (6.1%)	2	1/35 (2.9%)	1
Restless legs syndrome	0/30 (0%)	0	2/33 (6.1%)	2	1/35 (2.9%)	1
Burning sensation	0/30 (0%)	0	0/33 (0%)	0	2/35 (5.7%)	2
Psychiatric disorders
Anxiety	3/30 (10%)	3	2/33 (6.1%)	2	4/35 (11.4%)	4
Depression	3/30 (10%)	3	5/33 (15.2%)	5	1/35 (2.9%)	1
Insomnia	4/30 (13.3%)	4	1/33 (3%)	1	4/35 (11.4%)	4
Renal and urinary disorders
Pollakiuria	0/30 (0%)	0	1/33 (3%)	1	2/35 (5.7%)	2
Acute kidney injury	0/30 (0%)	0	2/33 (6.1%)	4	0/35 (0%)	0
Reproductive system and breast disorders
Breast pain	3/30 (10%)	3	1/33 (3%)	4	3/35 (8.6%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/30 (10%)	3	9/33 (27.3%)	10	6/35 (17.1%)	7
Cough	2/30 (6.7%)	2	8/33 (24.2%)	8	7/35 (20%)	9
Nasal congestion	1/30 (3.3%)	1	2/33 (6.1%)	4	4/35 (11.4%)	4
Oropharyngeal pain	1/30 (3.3%)	1	1/33 (3%)	1	2/35 (5.7%)	2
Pleural effusion	0/30 (0%)	0	3/33 (9.1%)	4	0/35 (0%)	0
Upper-airway cough syndrome	1/30 (3.3%)	1	2/33 (6.1%)	2	1/35 (2.9%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/30 (3.3%)	1	5/33 (15.2%)	5	6/35 (17.1%)	6
Pruritus	1/30 (3.3%)	1	3/33 (9.1%)	3	4/35 (11.4%)	5
Erythema	0/30 (0%)	0	4/33 (12.1%)	21	3/35 (8.6%)	4
Rash	1/30 (3.3%)	1	3/33 (9.1%)	3	3/35 (8.6%)	4
Rash maculo-papular	1/30 (3.3%)	4	2/33 (6.1%)	4	1/35 (2.9%)	1
Vascular disorders
Hypertension	2/30 (6.7%)	2	2/33 (6.1%)	2	1/35 (2.9%)	7
Hot flush	2/30 (6.7%)	2	2/33 (6.1%)	2	0/35 (0%)	0
Thrombophlebitis superficial	0/30 (0%)	0	1/33 (3%)	1	3/35 (8.6%)	7
Hypotension	1/30 (3.3%)	1	0/33 (0%)	0	2/35 (5.7%)	2

Limitations/Caveats

Limitations of this study are the small sample size and open-label design. Antitumor outcomes were not the primary endpoints.

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Certain Agreements

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

The investigator will submit results communications for review by the sponsor at least 60 days prior to expected submission to the intended publisher or meeting committee. This review period may be shortened upon mutual consent. The sponsor may request modification of any publication, presentation or use by the investigator if such activity may jeopardize a patent application, an existing patent, or other proprietary rights.