Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Docetaxel for Metastatic Non-Small Cell Lung Cancer (NSCLC) (PRESERVE 4)

Sponsor

G1 Therapeutics, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT04863248

Collaborator

(none)

Enrollment

Locations

Arms

9.6

Actual Duration (Months)

0.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 trial evaluating the effect of trilaciclib on overall survival when administered prior to docetaxel in patients with mNSCLC treated in the 2nd or 3rd line setting.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Non-Small Cell Lung Cancer NSCLC Lung Cancer	Drug: Trilaciclib Drug: Placebo Drug: Docetaxel	Phase 2

Detailed Description

Patients must have documented disease progression during or after one or two lines of systemic therapy for recurrent or metastatic NSCLC. Prior treatment must have included, either in the same line or as separate lines of therapy: 1) a maximum of 1 line of platinum-containing chemotherapy for recurrent/metastatic disease and 2) a maximum of 1 line of a locally approved/authorized programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) containing regimen for recurrent/metastatic disease.

Patients will be randomly assigned (1:1) to receive trilaciclib or placebo intravenously (IV) prior to docetaxel on Day 1 of each 21-day cycle.

The study will include a screening phase, a treatment phase and a survival follow-up phase. The patient may continue to receive treatment on study until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation by Investigator, or the end of the trial, whichever occurs first.

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Randomized, Double-blind, Clinical Trial of Trilaciclib Versus Placebo in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Treated With Docetaxel in the 2nd/3rd Line Setting (PRESERVE 4)

Actual Study Start Date :

Apr 16, 2021

Actual Primary Completion Date :

Feb 2, 2022

Actual Study Completion Date :

Feb 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: trilaciclib + docetaxel Patients will receive trilaciclib administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.	Drug: Trilaciclib Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle. Other Names: COSELA G1T28 Drug: Docetaxel Docetaxel administered IV on Day 1 of each 21-day cycle. Other Names: Taxotere Docefrez
Placebo Comparator: placebo + docetaxel Patients will receive placebo administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.	Drug: Placebo Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle. Other Names: 0.9% normal saline 5 % Dextrose in water (D5W) Drug: Docetaxel Docetaxel administered IV on Day 1 of each 21-day cycle. Other Names: Taxotere Docefrez

Arm

Intervention/Treatment

Experimental: trilaciclib + docetaxel

Patients will receive trilaciclib administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.

Drug: Trilaciclib

Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.

Other Names:

COSELA

G1T28

Drug: Docetaxel

Docetaxel administered IV on Day 1 of each 21-day cycle.

Other Names:

Taxotere

Docefrez

Placebo Comparator: placebo + docetaxel

Patients will receive placebo administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.

Drug: Placebo

Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.

Other Names:

0.9% normal saline

5 % Dextrose in water (D5W)

Drug: Docetaxel

Docetaxel administered IV on Day 1 of each 21-day cycle.

Other Names:

Taxotere

Docefrez

Outcome Measures

Primary Outcome Measures

Effect of trilaciclib on Overall Survival (OS) compared with placebo [From the date of randomization to the date of death for patients who died in the study due to any cause, or to the last contact date known to be alive for those who survived as of the data cutoff date, assessed up to 30 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on overall survival (OS) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

Secondary Outcome Measures

Effect of trilaciclib on Progression Free Survival (PFS) compared with placebo [From date of randomization to the date of documented radiologic PD per RECIST v1.1 or date of death regardless of the cause, whichever comes first, for those who had the events. Otherwise, PFS is calculated per censoring rules, assessed up to 30 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on progression free survival (PFS) in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on other anti-tumor endpoints compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on objective response rate (ORR) and duration of objective response (DOR) in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on the neutrophil lineage compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on duration of severe (grade 4) neutropenia in cycle 1, occurrence of severe (grade 4) neutropenia, occurrence of febrile neutropenia AEs, and occurrence of granulocyte colony-stimulating factor (G-CSF) administration in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on the red blood cell (RBC) lineage compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence of grade 3 or 4 decreased hemoglobin laboratory values, red blood cell (RBC) transfusions on or after week 5 (occurrence and number of transfusions), occurrence of erythropoiesis stimulating agent (ESA) administration in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on the platelet lineage compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence of grade 3 or 4 decreased platelet count laboratory values and platelet transfusions (occurrence and number of transfusions) in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on chemotherapy dosing compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on all-cause dose reductions (occurrence and number of reductions) and all-cause cycle delays (occurrence and number of delays) in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Effect of trilaciclib on hospitalizations due to chemotherapy induced myelosuppression compared with placebo [From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence and number of hospitalizations due to chemotherapy induced myelosuppression in patients with metastatic NSCLC receiving docetaxel in the second or third line.
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 [Time from date of first dose of trilaciclib/placebo and docetaxel through 30 days following the last dose of trilaciclib/placebo and docetaxel, assessed up to 30 months.]
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence and severity of adverse events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5, study treatment discontinuation due to adverse events (AEs), and trilaciclib adverse events of special interest (AESI) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years of age at the time of signing the informed consent.
Histologically or cytologically confirmed metastatic NSCLC (squamous or nonsquamous) with no known actionable driver mutations (ex. EGFR, ROS1, ALK).

Patients must have had documented disease progression during or after 1 or 2 lines of systemic treatment for recurrent or metastatic disease.
Two components of treatment must have been received in the same line or as separate lines of therapy: (i) a maximum of 1 line of platinum-containing chemotherapy regimen for recurrent/metastatic disease, and (ii) a maximum of 1 line of a locally approved/authorized PD-1/PD-L1 mAb containing regimen for recurrent/metastatic disease.
Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy. Maintenance therapy is defined as therapy given within 42 days after the last dose of platinum-based chemotherapy in patients with ongoing clinical benefit (complete response [CR], partial response [PR] or stable disease [SD]).

Measurable or non-measurable disease per RECIST v1.1.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting NSCLC must be available to send to the Sponsor, within the specified timeframe, for planned retrospective biomarker analyses.
Adequate organ function defined by the normal laboratory values.

Exclusion Criteria:

Prior therapy with docetaxel.
Any contraindication to the administration of docetaxel at the discretion of the investigator.
Mixed NSCLC/SCLC, or lung tumors whose predominant histology is sarcomatoid, or neuroendocrine.
Any chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or prostate-specific antigen (PSA) persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.
Any radiotherapy within 2 weeks prior to the first dose of trilaciclib/placebo.
Presence of central nervous system (CNS) metastases requiring immediate treatment with radiation therapy or steroids (i.e., patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of trilaciclib/placebo).
Presence of leptomeningeal disease.
Significant third-space fluid retention (ex. ascites or pleural effusion) not amenable to required repeat drainage.
QT corrected using Fridericia's formula (QTcF) interval >480 msec at screening (confirmed on repeat). For patients with ventricular pacemakers, QTcF >500 msec.
Symptomatic peripheral neuropathy.
History of interstitial lung disease (ILD).
Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer &Research Centers	Phoenix	Arizona	United States	85028
2	Valkyrie Clinical Trials	Los Angeles	California	United States	90067
3	Desert Hematology Oncology Medical Group, Inc	Rancho Mirage	California	United States	92270
4	Innovative Clinical Research Institute - Oncology	Whittier	California	United States	90602
5	Mid-Florida Hematology Oncology	Orange City	Florida	United States	32763
6	Indiana University Health Goshen Cancer Center	Goshen	Indiana	United States	46526
7	St. Louis Cancer Care, LLP	Bridgeton	Missouri	United States	63044
8	Summit Medical Group	Florham Park	New Jersey	United States	07932
9	Regional Cancer Car Associates LLC	Little Silver	New Jersey	United States	07739
10	Gettysburg Cancer Center	Gettysburg	Pennsylvania	United States	17325
11	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
12	Millennium Oncology	Houston	Texas	United States	77090