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Calderasib plus cetuximab and chemotherapy for KRAS G12C colorectal cancer

A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084, Cetuximab, and mFOLFOX6 Versus mFOLFOX6 With or Without Bevacizumab as First-line Treatment of Participants With KRAS G12C-mutant, Locally Advanced Unresectable or Metastatic Colorectal Cancer (KANDLELIT-012)

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT06997497

This trial will test whether adding calderasib and cetuximab to mFOLFOX6 helps people with unresectable locally advanced or metastatic colorectal cancer that has a KRAS G12C mutation live longer without their cancer growing.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment477 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionsbevacizumab, cetuximab
Locations161 sites (Los Angeles, California and 160 other locations)
Trial IDNCT06997497 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Adults with histologically confirmed unresectable locally advanced or metastatic colorectal adenocarcinoma whose tumor tests positive for a KRAS G12C mutation and who meet the trial's treatment-history criteria (for example, no prior systemic therapy in Part 2) are ideal candidates.

Not a fit: Patients without a KRAS G12C mutation, those eligible for curative surgical resection, or those with uncontrolled comorbidities or active infections are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could prolong the time patients live without their colorectal cancer progressing and may improve outcomes for those with KRAS G12C tumors.

How similar studies have performed: Other trials of KRAS G12C inhibitors combined with EGFR antibodies have shown promising but modest activity in colorectal cancer compared with lung cancer, so combination strategies remain under active study.

Eligibility criteria

Show full inclusion / exclusion criteria 
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
* Tumor tissue 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 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
* 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 this trial is running

Los Angeles, California and 160 other locations

+111 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Colon AdenocarcinomaRectal Adenocarcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.