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

• ClinicalTrials.gov Identifier: NCT04863248
• Recruitment Status: Terminated
• First Posted: April 28, 2021
• Last Update Posted: March 2, 2022
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

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 (Clinical Trial)
• 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: April 16, 2021
• Actual Primary Completion Date: February 2, 2022
• Actual Study Completion Date: February 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

Outcome Measures

Primary Outcome Measures :

1. Effect of trilaciclib on Overall Survival (OS) compared with placebo [ Time Frame: 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 :

1. Effect of trilaciclib on Progression Free Survival (PFS) compared with placebo [ Time Frame: 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.
2. Effect of trilaciclib on other anti-tumor endpoints compared with placebo [ Time Frame: 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.
3. Effect of trilaciclib on the neutrophil lineage compared with placebo [ Time Frame: 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.
4. Effect of trilaciclib on the red blood cell (RBC) lineage compared with placebo [ Time Frame: 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.
5. Effect of trilaciclib on the platelet lineage compared with placebo [ Time Frame: 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.
6. Effect of trilaciclib on chemotherapy dosing compared with placebo [ Time Frame: 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.
7. Effect of trilaciclib on hospitalizations due to chemotherapy induced myelosuppression compared with placebo [ Time Frame: 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.
8. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

  1. Patients must have had documented disease progression during or after 1 or 2 lines of systemic treatment for recurrent or metastatic disease.
  2. 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.
  3. 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

United States, Arizona

Ironwood Cancer &Research Centers

Phoenix, Arizona, United States, 85028

United States, California

Valkyrie Clinical Trials

Los Angeles, California, United States, 90067

Desert Hematology Oncology Medical Group, Inc

Rancho Mirage, California, United States, 92270

Innovative Clinical Research Institute - Oncology

Whittier, California, United States, 90602

United States, Florida

Mid-Florida Hematology Oncology

Orange City, Florida, United States, 32763

United States, Indiana

Indiana University Health Goshen Cancer Center

Goshen, Indiana, United States, 46526

United States, Missouri

St. Louis Cancer Care, LLP

Bridgeton, Missouri, United States, 63044

United States, New Jersey

Summit Medical Group

Florham Park, New Jersey, United States, 07932

Regional Cancer Car Associates LLC

Little Silver, New Jersey, United States, 07739

United States, Pennsylvania

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States, 17325

United States, Tennessee

University of Tennessee Medical Center

Knoxville, Tennessee, United States, 37920

United States, Texas

Millennium Oncology

Houston, Texas, United States, 77090

Sponsors and Collaborators

G1 Therapeutics, Inc.

Investigators

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

More Information

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04863248
• Other Study ID Numbers: G1T28-210; 2021-000186-32 ( EudraCT Number )
• First Posted: April 28, 2021
• Last Update Posted: March 2, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by G1 Therapeutics, Inc.:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Docetaxel; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action