Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT05789082Sponsor: Hoffmann-La RocheLast updated: 2026-06-15

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Confirmation of Biomarker eligibility * Pre-treatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin-fixed, paraffin embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * Histologically or cytologically documented locally advanced unresectable or metastatic NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy * No prior systemic treatment for advanced unresectable or metastatic NSCLC * Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Additionally, for participants in cohort D, measurable brain metastases defined as at least 5 millimeters and twice the slice thickness, but less than 20 mm, that is asymptomatic and does not require local therapy at the time of enrollment. Exclusion Criteria: * Known concomitant second oncogenic driver with available targeted treatment * Squamous cell histology NSCLC * Symptomatic, untreated, or actively progressing CNS metastases (Cohorts A, B, and C) * Prior treatment with a KRAS G12C inhibitor * Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only) * History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, active tuberculosis, significant cardiovascular disease within 3 months prior to initiation of study treatment * History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer * Uncontrolled tumor related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia * Co-morbid condition that is an absolute contraindication to treatment with corticosteroids * Inability or unwillingness to take prophylactic treatments such as corticosteroids, anti-emetics, folic acid, or vitamin B12 supplementation. * Participants with brain metastases for whom complete surgical resections is clinically appropriate

Study locations (16)

City of Hope National Medical Center

Duarte, California, 91010

Withdrawn

City of Hope - Seacliff

Huntington Beach, California, 92648

Withdrawn

City of Hope at Irvine Lennar

Irvine, California, 92618

Withdrawn

UCSD Moores Cancer Center

La Jolla, California, 92093

Withdrawn

City of Hope - Long Beach Elm

Long Beach, California, 90813

Withdrawn

Yale Cancer Center

New Haven, Connecticut, 06520

Recruiting

Florida Cancer Specialists - SOUTH - SCRI - PPDS

Fort Myers, Florida, 33901-8108

Recruiting

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida, 33705-1400

Recruiting

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida, 33401-3406

Recruiting

NYU Langone Hospital - Long Island

Mineola, New York, 11501

Recruiting

NYU Cancer Center

New York, New York, 10016

Recruiting

Mount SInai Medical Center

New York, New York, 10029

Recruiting

Montefiore Medical Center - Montefiore Medical Park

The Bronx, New York, 10461

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

Oncology & Hematology Associates of Southwest Virginia, Inc

Blacksburg, Virginia, 24060

Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502

Recruiting
A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation | Cancerify