A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer

Sponsor: Hoffmann-La Roche

Sponsor score: 40

ClinicalTrials ID:NCT06793215

This study assesses the efficacy and safety of divarasib and pembrolizumab in treating KRAS G12C-mutated advanced NSCLC. Eligible participants must have an ECOG status of 0-1, measurable disease, and no prior systemic treatment. Exclusions include other oncogenic drivers and recent anti-cancer therapies. Interventions include oral divarasib and IV pembrolizumab, pemetrexed, carboplatin, or cisplatin.

Patient Parameters

Program Overview

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).

Eligibility Criteria

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
  • Measurable disease, as defined by RECIST v1.1
  • No prior systemic treatment for advanced or metastatic NSCLC
  • Documentation of the presence of a KRAS G12C mutation
  • Documentation of known PD-L1 expression status in tumor tissue
  • Availability of a representative tumor specimen
  • Adequate end-organ function
  • Eligible to receive a platinum-based chemotherapy regimen

Exclusion Criteria Related to NSCLC:

  • Known concomitant second oncogenic driver with available targeted treatment
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to randomization
  • History of leptomeningeal disease
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)

Exclusion Criteria Related to Current or Prior Treatments:

  • Any anti-cancer systemic therapy, including hormonal therapy, within 21 days prior to randomization, or is expected to require any other form of antineoplastic therapy while in the study
  • Radiation therapy including palliative RT to bone metastases within 2 weeks prior to randomization and RT to the lung >30Gy within 6 months prior to randomization
  • Prior treatment with KRAS G12C inhibitors or pan-KRAS/RAS inhibitors
  • Treatment with systemic immunosuppressive or immunostimulatory medications, including CD137 agonists and immune checkpoint inhibitors
  • Current treatment with medications that are well known to prolong the QT interval
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to randomization
  • Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to General Health:

  • History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival [OS] rate >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
  • Individuals with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis), malabsorption syndrome, conditions that would interfere with enteral absorption
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
  • Significant cardiovascular disease within 3 months prior to screening

Locations

FACILITYZIPCITYSTATE
Alaska Oncology and Hematology99508AnchorageAlaska
Marin Cancer Care Inc94904GreenbraeCalifornia
BioResearch Partner33013HialeahFlorida
Summit Cancer Care PC31405SavannahGeorgia
Hope and Healing Cancer Services60521HinsdaleIllinois
Profound Research, LLC48334Farmington HillsMichigan
Missouri Baptist Medical Center63131St LouisMissouri
San Juan Oncology Associates87401FarmingtonNew Mexico
Clinical Research Alliance11590WestburyNew York
Baptist Cancer Center38120MemphisTennessee

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