Divarasib plus pembrolizumab versus pembrolizumab with pemetrexed and platinum chemotherapy for first-line KRAS G12C advanced non-squamous non-small cell lung cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized Phase 3 trial enrolls adults with previously untreated, measurable, advanced or metastatic non-squamous NSCLC carrying a KRAS G12C mutation and an ECOG performance status of 0–1. Participants are randomized to receive divarasib with the PD-1 inhibitor pembrolizumab or the standard first-line regimen of pembrolizumab combined with pemetrexed and a platinum agent (carboplatin or cisplatin). Key requirements include documented KRAS G12C mutation, known PD-L1 status, available tumor tissue, and adequate organ function. Tumor response is monitored by imaging per RECIST v1.1 and safety and efficacy endpoints are compared between arms.

Why it matters

Who can join: the full rules

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

Where it's running

• Alaska Oncology and Hematology
  Anchorage, Alaska, United States Recruiting
• City of Hope - Phoenix
  Goodyear, Arizona, United States Recruiting
• Community Cancer Institute (CCI)
  Clovis, California, United States Recruiting
• Marin Cancer Care Inc
  Greenbrae, California, United States Recruiting
• UCI Health-CIACC
  Irvine, California, United States Recruiting
• UCLA Oncology Center
  Los Angeles, California, United States Recruiting

+249 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Reference Study ID Number: CO45042 https://forpatients.roche.com/ No attachments to email below.
• Email: global-roche-genentech-trials@gene.com
• Phone: 888-662-6728 (U.S. and Canada)

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• First-line treatment with pembrolizumab, pemetrexed, and platinum with or without zoldonrasib for metastatic non-squamous NSCLC

  This trial tests whether adding zoldonrasib to standard pembrolizumab and platinum chemotherapy helps people with untreated metastatic non-squamous NSCLC that has a RAS G12D mutation.

  Recruiting at 4 sites Phase 3 Revolution Medicines, Inc. · Anchorage, Alaska and 3 other locations · NCT07777822

• ABBV-1480 plus chemotherapy vs pembrolizumab plus chemotherapy as first-line treatment for locally advanced or metastatic non-small cell lung cancer

  This study tests whether ABBV-1480 with platinum-based chemotherapy can work better than pembrolizumab with chemotherapy for adults with certain stages of non-small cell lung cancer.

  Recruiting at 2 sites Phase 3 AbbVie · Fort Wayne, Indiana and 1 other locations · NCT07756645

• Adjuvant intismeran (V940) with or without pembrolizumab plus berahyaluronidase alfa for high‑risk Stage I non‑small cell lung cancer after surgery

  This trial will try intismeran (V940) alone or together with subcutaneous pembrolizumab plus berahyaluronidase alfa to help prevent recurrence in people with completely removed high‑risk Stage I non‑small cell lung cancer.

  Recruiting at 126 sites Phase 3 Merck Sharp & Dohme LLC · Sacramento, California and 125 other locations · NCT07513376

• Adjuvant calderasib with subcutaneous pembrolizumab plus berahyaluronidase alfa for completely resected KRAS G12C stage IIA–IIIB (N2) NSCLC

  This trial tests whether adding the oral KRAS G12C inhibitor calderasib to subcutaneous pembrolizumab plus berahyaluronidase alfa helps prevent recurrence in people with completely resected stage IIA–IIIB (N2) KRAS G12C non‑small cell lung cancer.

  Recruiting at 122 sites Phase 3 Merck Sharp & Dohme LLC · Ciudad Autónoma de Buenos Aires, Buenos Aires and 121 other locations · NCT07431827

• PF-08634404 plus chemotherapy versus pembrolizumab-based chemotherapy for advanced non-small cell lung cancer

  This will test whether PF-08634404 combined with chemotherapy works better than pembrolizumab plus chemotherapy for adults with locally advanced or metastatic non-small cell lung cancer who have not received prior treatment for their advanced disease.

  Recruiting at 464 sites Phase 3 Pfizer · Bullhead City, Arizona and 483 other locations · NCT07222566

• Calderasib plus subcutaneous pembrolizumab for KRAS G12C non-small cell lung cancer

  This trial will test whether adding the KRAS G12C drug calderasib to subcutaneous pembrolizumab helps people with advanced nonsquamous non‑small cell lung cancer live longer without the cancer growing compared with pembrolizumab plus chemotherapy.

  Recruiting at 221 sites Phase 3 Merck Sharp & Dohme LLC · Birmingham, Alabama and 224 other locations · NCT07190248

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.