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

Study Overview
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Brief Summary
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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 metastatic NSCLC treated in the 2nd or 3rd line setting.

Detailed Description
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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. This study was terminated by the Sponsor for non-safety reasons. At the time of study termination, 10 patients had been screened, 7 were randomized, and 2 of the 7 had discontinued from the study. In addition, it was decided that there would be no statistical analyses of the efficacy or safety data due to the limited number of patients treated (N=7).

Official Title
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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)

Conditions
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Metastatic Non-Small Cell Lung Cancer, NSCLC, Lung Cancer

Intervention / Treatment
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* Drug: Trilaciclib
* Drug: Placebo
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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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 (eg, 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 (eg, 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: trilaciclib + docetaxel<br>Patients will receive trilaciclib administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle. | Drug: Trilaciclib<br>* Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.<br>* Other names: G1T28;Drug: Docetaxel<br>* Docetaxel administered IV on Day 1 of each 21-day cycle.<br>* Other names: Docefrez;|
| Placebo Comparator: placebo + docetaxel<br>Patients will receive placebo administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle. | Drug: Placebo<br>* Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.<br>* Other names: 5% Dextrose in water (D5W);Drug: Docetaxel<br>* Docetaxel administered IV on Day 1 of each 21-day cycle.<br>* Other names: Docefrez;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | 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. | 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 9 months and 2 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trilaciclib, Lung Cancer, Non-Small Cell Lung Cancer, PRESERVE 4, CDK 4/6 Inhibitor, cyclin-dependent kinase 4/6 inhibitor, Preserve, NSCLC, solid tumors, chemotherapy, metastatic, myeloprotection, advanced, stage 4, lung, docetaxel, COSELA, G1T28