A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation
Summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of single-agent divarasib or combined with other anti-cancer therapies in participants with previously untreated, advanced or metastatic non-small cell lung cancer (NSCLC).
Arms & interventions
- DrugDivarasib
Participants will receive divarasib orally (PO), QD on days 1-21 of each 21-day cycle.
- DrugPembrolizumab
Participants will receive a 200 mg IV infusion of pembrolizumab Q3W on Day 1 of each 21-day cycle.
- DrugCarboplatin
Participants will receive IV carboplatin Q3W for four 21-day cycles.
- DrugCisplatin
Participants will receive IV cisplatin Q3W for four 21-day cycles.
- DrugPemetrexed
Participants will receive IV pemetrexed Q3W.
Outcome measures
Primary
Percentage of Participants with Adverse Events (AEs)
Time frame: Baseline until 60 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately 5 years)
Secondary
Objective Response Rate (ORR)
Time frame: Approximately 5 years
Duration of Response (DOR)
Time frame: Approximately 5 years
Progression Free Survival (PFS)
Time frame: Approximately 5 years
Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Side Effects as Assessed Through the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time frame: Approximately 5 years
Change from Baseline in Symptomatic Side Effects, as Assessed Through use of the PRO-CTCAE
Time frame: Baseline up to approximately 5 years
Percentage of Participants Reporting "Frequent" or "Almost Constant" Diarrhea During the First Three Cycles of Treatment According to the PRO-CTCAE Criteria
Time frame: Approximately 5 years
Percentage of Participants Reporting "Severe" or "Very Severe" Nausea or Vomiting During the First Three Cycles of Treatment According to the PRO-CTCAE
Time frame: Approximately 5 years
Frequency of Participant's Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the Single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46)
Time frame: Approximately 5 years
Plasma or CSF Concentration of Divarasib at Specified Timepoints
Time frame: Approximately 5 years
Identification of Divarasib Recommended Dose
Time frame: Approximately 5 years
Central Nervous System (CNS) Response
Time frame: Approximately 5 years
Eligibility criteria
Study locations (16)
City of Hope National Medical Center
Duarte, California, 91010
City of Hope - Seacliff
Huntington Beach, California, 92648
City of Hope at Irvine Lennar
Irvine, California, 92618
UCSD Moores Cancer Center
La Jolla, California, 92093
City of Hope - Long Beach Elm
Long Beach, California, 90813
Yale Cancer Center
New Haven, Connecticut, 06520
Florida Cancer Specialists - SOUTH - SCRI - PPDS
Fort Myers, Florida, 33901-8108
Florida Cancer Specialists - NORTH - SCRI - PPDS
St. Petersburg, Florida, 33705-1400
Florida Cancer Specialists - EAST - SCRI - PPDS
West Palm Beach, Florida, 33401-3406
NYU Langone Hospital - Long Island
Mineola, New York, 11501
NYU Cancer Center
New York, New York, 10016
Mount SInai Medical Center
New York, New York, 10029
Montefiore Medical Center - Montefiore Medical Park
The Bronx, New York, 10461
MD Anderson Cancer Center
Houston, Texas, 77030
Oncology & Hematology Associates of Southwest Virginia, Inc
Blacksburg, Virginia, 24060
Virginia Oncology Associates
Norfolk, Virginia, 23502