Lung Cancer, Metastatic Non-Small Cell Lung Cancer, NSCLC
Conditions
Keywords
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
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 metastatic NSCLC 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. 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).
Interventions
DRUGTrilaciclib
Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
DRUGPlacebo
Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
DRUGDocetaxel
Docetaxel administered IV on Day 1 of each 21-day cycle.
Sponsors
G1 Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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). 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 (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 9 months and 2 days. | 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. |
Countries
United States
Participant flow
Recruitment details
Due to the rapidly evolving treatment landscape for patients with metastatic NSCLC, G1 Therapeutics announced the decision to terminate this study on 03 November 2021. This study was not terminated for reasons related to safety. At the time of study termination, 10 patients had been screened, 7 were randomized, and 2 of the 7 had already discontinued from the study.
Pre-assignment details
Of the 10 patients enrolled, 3 were screen failures and 7 patients were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Trilaciclib + Docetaxel Patients will receive trilaciclib administered IV no more than 4 hours prior to docetaxel administered IV on Day 1 of each 21-day cycle.
Trilaciclib: Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
Docetaxel: Docetaxel administered IV on Day 1 of each 21-day cycle. | 4 |
| Placebo + Docetaxel Patients will receive placebo administered IV no more than 4 hours prior to docetaxel administered IV on Day 1 of each 21-day cycle.
Placebo: Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
Docetaxel: Docetaxel administered IV on Day 1 of each 21-day cycle. | 3 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Sponsor Terminated | 4 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Trilaciclib + Docetaxel | Placebo + Docetaxel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 58.3 years STANDARD_DEVIATION 11.47 | 62.7 years STANDARD_DEVIATION 2.52 | 60.1 years STANDARD_DEVIATION 8.57 |
| ECOG Score 0 | 1 Participants | 1 Participants | 2 Participants |
| ECOG Score 1 | 2 Participants | 2 Participants | 4 Participants |
| ECOG Score 2 | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Histopathologic Type Adenocarcinoma | 3 Participants | 2 Participants | 5 Participants |
| Histopathologic Type Squamous Cell Carcinoma | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Stage at Diagnosis IV | 4 Participants | 3 Participants | 7 Participants |
| Stage at Diagnosis Unknown | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 3 |
| other Total, other adverse events | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 1 / 4 | 3 / 3 |
Outcome results
Primary
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 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 9 months and 2 days.
Population: 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).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trilaciclib + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE of Grade >= 3 | 2 participants |
| Trilaciclib + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE of Grade >= 4 | 0 participants |
| Trilaciclib + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE | 4 participants |
| Placebo + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE | 3 participants |
| Placebo + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE of Grade >= 3 | 3 participants |
| Placebo + Docetaxel | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 | Any AE of Grade >= 4 | 3 participants |