Calderasib plus cetuximab and chemotherapy for KRAS G12C colorectal 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 Phase 3 trial adds the KRAS G12C inhibitor calderasib and the EGFR antibody cetuximab to standard mFOLFOX6 chemotherapy for people with unresectable locally advanced or metastatic colorectal adenocarcinoma that harbors a KRAS G12C mutation. The study has two parts, with Part 2 enrolling patients who have not received prior systemic therapy for their advanced disease. Participants receive calderasib plus cetuximab alongside mFOLFOX6 (oxaliplatin, leucovorin, and 5‑fluorouracil) and are compared to a control arm of mFOLFOX6 with or without bevacizumab. Key outcomes include safety, tolerability, and progression-free survival to see if the combination delays cancer growth or spread.

Why it matters

Who can join: the full rules

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
* Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
* Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
* Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
* Has active infection requiring systemic therapy
* Has not adequately recovered from major surgery or have ongoing surgical complications
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

Where it's running

• Mayo Clinic - Arizona ( Site 0090)
  Phoenix, Arizona, United States Recruiting
• Orange Coast Memorial Medical Center ( Site 2007)
  Fountain Valley, California, United States Recruiting
• Los Angeles Hematology Oncology Medical Group ( Site 0084)
  Los Angeles, California, United States Recruiting
• University of California Davis (UC Davis) Comprehensive Cancer Center ( Site 2021)
  Sacramento, California, United States Recruiting
• UCLA Hematology/Oncology - Santa Monica ( Site 0088)
  Santa Monica, California, United States Recruiting
• University of Colorado Health - Harmony-Cancer Care and Hematology - Ft. Collins ( Site 0087)
  Fort Collins, Colorado, United States Recruiting

+195 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Toll Free Number
• Email: Trialsites@msd.com
• Phone: 1-888-577-8839

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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.