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RecruitingInterventionalPhase 3

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)

NCT ID: NCT06997497Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-15

Summary

Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C. Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies. The goals of this study are to learn: * About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments * If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.

Detailed description

This study will have 2 parts.

Arms & interventions

  • DrugCalderasib

    Oral tablet

  • DrugOxaliplatin

    Per label

  • DrugLeucovorin/levofolinate calcium

    Per label

  • Drug5-Fluorouracil

    Per label

  • BiologicalCetuximab

    Per label

  • DrugBevacizumab

    Per label

  • DrugBevacizumab biosimilar

    Per label

Outcome measures

Primary

  • Number of Participants Experiencing Dose-Limiting Toxicity (DLT)

    A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration.

    Time frame: Up to approximately 28 days

  • Part 1: Number of Participants Who Experience an Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to approximately 44 months

  • Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to approximately 44 months

  • Progression Free Survival (PFS)

    PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.

    Time frame: Up to approximately 44 months

Secondary

  • Objective Response Rate (ORR)

    Time frame: Up to approximately 3 years

  • Overall Survival (OS)

    Time frame: Up to approximately 5 years

  • Duration of Response (DOR)

    Time frame: Up to approximately 4 years

  • Part 2: Number of Participants with an Adverse Event (AE)

    Time frame: Up to approximately 5 years

  • Part 2: Number of Participants who Discontinue Study Treatment Due to an AE

    Time frame: Up to approximately 5 years

  • Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

    Time frame: Baseline and up to approximately 5 years

  • Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score

    Time frame: Baseline and up to approximately 5 years

  • Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score

    Time frame: Baseline and up to approximately 5 years

  • Change from Baseline in the EORTC-QLQ-C30 Appetite Loss (Item 13) Score

    Time frame: Baseline and up to approximately 5 years

  • Change from Baseline in the EORTC-Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

    Time frame: Baseline and up to approximately 5 years

  • Time to First Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score

    Time frame: Baseline and up to approximately 5 years

  • TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

    Time frame: Baseline and up to approximately 5 years

  • TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score

    Time frame: Baseline and up to approximately 5 years

  • TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score

    Time frame: Baseline and up to approximately 5 years

  • TTD in EORTC QLQ-CR29 Bloating (Item 37) Score

    Time frame: Baseline and up to approximately 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (27)

Los Angeles Hematology Oncology Medical Group ( Site 0084)

Los Angeles, California, 90017

Recruiting
Study Coordinator · Contact

University of Colorado Health - Harmony-Cancer Care and Hematology - Ft. Collins ( Site 0087)

Fort Collins, Colorado, 80528

Recruiting
Study Coordinator · Contact

Rocky Mountain Cancer Centers (RMCC) ( Site 8000)

Lone Tree, Colorado, 80124

Recruiting
Study Coordinator · Contact

Florida Cancer Specialists - South ( Site 7002)

Fort Myers, Florida, 33901

Recruiting
Study Coordinator · Contact

Orlando Health Cancer Institute ( Site 0065)

Orlando, Florida, 32806

Recruiting
Study Coordinator · Contact

Florida Cancer Specialists - North ( Site 7001)

St. Petersburg, Florida, 33705

Recruiting
Study Coordinator · Contact

Florida Cancer Specialists - East ( Site 7000)

West Palm Beach, Florida, 33401

Recruiting
Study Coordinator · Contact

University of Iowa ( Site 0074)

Iowa City, Iowa, 52242

Recruiting
Study Coordinator · Contact

University of Kentucky ( Site 0055)

Lexington, Kentucky, 40536

Recruiting
Study Coordinator · Contact

Norton Cancer Institute, Audubon Hospital Campus ( Site 0054)

Louisville, Kentucky, 40217

Recruiting
Study Coordinator · Contact

Greater Baltimore Medical Center ( Site 0068)

Baltimore, Maryland, 21204

Recruiting
Study Coordinator · Contact

Hattiesburg Clinic ( Site 0064)

Hattiesburg, Mississippi, 39401

Recruiting
Study Coordinator · Contact

Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 2000)

Billings, Montana, 59102

Recruiting
Study Coordinator · Contact

University Of Nebraska Medical Center ( Site 0078)

Omaha, Nebraska, 68198

Recruiting
Study Coordinator · Contact

Renown Regional Medical Center ( Site 0056)

Reno, Nevada, 89502

Recruiting
Study Coordinator · Contact

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0060)

Hackensack, New Jersey, 07601

Recruiting
Study Coordinator · Contact

San Juan Oncology Associates, P.C ( Site 2011)

Farmington, New Mexico, 87401

Recruiting
Study Coordinator · Contact

Ellis Hospital ( Site 0098)

Schenectady, New York, 12308

Recruiting
Study Coordinator · Contact

Miami Valley Hospital South ( Site 0075)

Centerville, Ohio, 45459

Recruiting
Study Coordinator · Contact

Texas Oncology - DFW ( Site 8002)

Dallas, Texas, 75246

Recruiting
Study Coordinator · Contact

UT Southwestern Medical Center ( Site 0059)

Dallas, Texas, 75390

Recruiting
Study Coordinator · Contact

Texas Oncology - Northeast Texas ( Site 8001)

Denison, Texas, 75020

Recruiting
Study Coordinator · Contact

Texas Oncology - San Antonio ( Site 8004)

San Antonio, Texas, 78240

Recruiting
Study Coordinator · Contact

Community Cancer Trials of Utah ( Site 0086)

Ogden, Utah, 84405

Recruiting
Study Coordinator · Contact

University of Virginia ( Site 0080)

Charlottesville, Virginia, 22908

Recruiting
Study Coordinator · Contact

Virginia Cancer Specialists, PC ( Site 0069)

Fairfax, Virginia, 22031

Recruiting
Study Coordinator · Contact

Fred Hutchinson Cancer Center ( Site 0076)

Seattle, Washington, 98109

Recruiting
Study Coordinator · Contact