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.

Tracking Information

• First Submitted Date: April 16, 2021
• First Posted Date: April 28, 2021
• Last Update Posted Date: March 2, 2022
• Actual Study Start Date: April 16, 2021
• Actual Primary Completion Date: February 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 23, 2021)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 23, 2021)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Metastatic Non-Small Cell Lung Cancer
• NSCLC
• Lung Cancer

Intervention

• 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: 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

Study Arms

• Experimental: trilaciclib + docetaxel
  Patients will receive trilaciclib administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.
  Interventions:

  • Drug: Trilaciclib
  • Drug: Docetaxel
• Placebo Comparator: placebo + docetaxel
  Patients will receive placebo administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.
  Interventions:

  • Drug: Placebo
  • Drug: Docetaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 11, 2022): 7
• Original Estimated Enrollment (submitted: April 23, 2021): 146
• Actual Study Completion Date: February 2, 2022
• Actual Primary Completion Date: February 2, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04863248
• Other Study ID Numbers: G1T28-210; 2021-000186-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: G1 Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: G1 Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: G1 Therapeutics, Inc.
• Verification Date: February 2022