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Recruiting Phase 3

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

NCT06793215 · tracked via the Priya Life Science Italy tracker
Phase
Phase 3
Started
2025-10-24
Last updated
2026-10-06

Condition(s) studied

Non-Small Cell Lung CancerKRAS G12C Lung Cancer

Investigational drug(s) / intervention(s)

Divarasib →Pembrolizumab →Pemetrexed →Carboplatin →Cisplatin →

Divarasib: Divarasib will be administered orally QD

Pembrolizumab: Pembrolizumab will be administered via IV infusion Q3W

Pemetrexed: Pemetrexed will be administered via IV infusion Q3W

Carboplatin: Carboplatin will be administered via IV infusion Q3W

Cisplatin: Cisplatin will be administered via IV infusion Q3W

Study summary

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

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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

Primary outcome measure(s)

  • Progression-Free Survival (PFS) — Up to approximately 5 years
    PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)
  • Overall Survival (OS) — Up to approximately 5 years
    OS is defined as the time from randomization to death from any cause

Trial sites (288)

FacilityCityRegionStatus
Alaska Oncology and Hematology Anchorage Alaska Recruiting
City of Hope - Phoenix Goodyear Arizona Recruiting
Community Cancer Institute (CCI) Clovis California Recruiting
Marin Cancer Care Inc Greenbrae California Recruiting
UCI Health-CIACC Irvine California Recruiting
UCLA Oncology Center Los Angeles California Recruiting
Hoag Memorial Hospital Newport Beach California Recruiting
University of California Irvine Orange California Recruiting
Palo Alto Medical Foundation Research Center Palo Alto California Recruiting
Sutter Institute for Medical Research Roseville California Recruiting
California Pacific Medical Center San Francisco California Recruiting
UC Health Oncology Research Colorado Springs Colorado Recruiting
Poudre Valley Health Care, Inc. d/b/a Poudre Valley Health System Fort Collins Colorado Recruiting
Hartford Hospital Hartford Connecticut Recruiting
Florida Cancer Specialists - SOUTH - SCRI - PPDS Fort Myers Florida Recruiting
University of Florida Health at Shands Gainesville Florida Recruiting
BioResearch Partner Hialeah Florida Recruiting
Memorial Healthcare System - Memorial Regional Hospital Hollywood Florida Recruiting
Sylvester Comprehensive Cancer Center Miami Florida Recruiting
Advent Health Orlando Orlando Florida Recruiting
Ascension Sacred Heart Pensacola Florida Recruiting
Florida Cancer Specialists - NORTH - SCRI - PPDS St. Petersburg Florida Recruiting
Florida Cancer Specialists - EAST - SCRI - PPDS West Palm Beach Florida Recruiting
Piedmont Cancer Institute, PC Atlanta Georgia Recruiting
City of Hope® Atlanta Newnan Georgia Recruiting
Summit Cancer Care PC Savannah Georgia Recruiting
St. Luke's Cancer Institute Boise Idaho Recruiting
Affiliated Oncologists, LLC Chicago Ridge Illinois Recruiting
Hope and Healing Cancer Services Hinsdale Illinois Withdrawn
City of Hope® Cancer Center Chicago Zion Illinois Recruiting
Mission Cancer + Blood - IMMC Des Moines Iowa Recruiting
University of Iowa Iowa City Iowa Recruiting
Saint Agnes Hospital - Baltimore - Hunt - PPDS Baltimore Maryland Recruiting
Walter Reed National Military Medical Center Bethesda Maryland Recruiting
Massachusetts General Hospital Boston Massachusetts Recruiting
University of Massachusetts Memorial Medical Center Worcester Massachusetts Recruiting
Profound Research, LLC Farmington Hills Michigan Recruiting
Metro-Minnesota Community Oncology Research Consortium Saint Louis Park Minnesota Recruiting
Missouri Baptist Medical Center St Louis Missouri Recruiting
NHO Revive Research Institute Lincoln Nebraska Recruiting

+ 248 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06793215 on ClinicalTrials.gov ↗ ← All trials in Italy