Clinical trial NCT06997497: A Clinical Study of MK-1084 With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Colon Adenocarcinoma
Rectal Adenocarcinoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2025-05-30
Enrollment: 477
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 MK-1084 (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. MK-1084 and cetuximab are targeted therapies.

The goals of this study are to learn:

* About the safety of MK-1084 with cetuximab and mFOLFOX6 and if people tolerate the treatments
* If people who receive MK-1084 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.

Eligibility 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

Primary outcomes:
measure: Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
timeFrame: Up to approximately 28 days
measure: Part 1: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 6 years
measure: Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 6 years
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 5 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 4 years
measure: Part 2: Number of Participants with an Adverse Event (AE)
timeFrame: Up to approximately 6 years
measure: Part 2: Number of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 6 years
measure: 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
timeFrame: Baseline and up to approximately 6 years
measure: Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score
timeFrame: Baseline and up to approximately 6 years
measure: Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score
timeFrame: Baseline and up to approximately 6 years
measure: Change from Baseline in the EORTC-QLQ-C30 Appetite Loss (Item 13) Score
timeFrame: Baseline and up to approximately 6 years
measure: Change from Baseline in the EORTC-Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
timeFrame: Baseline and up to approximately 6 years
measure: Time to First Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
timeFrame: Baseline and up to approximately 6 years
measure: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
timeFrame: Baseline and up to approximately 6 years
measure: TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score
timeFrame: Baseline and up to approximately 6 years
measure: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
timeFrame: Baseline and up to approximately 6 years
measure: TTD in EORTC QLQ-CR29 Bloating (Item 37) Score
timeFrame: Baseline and up to approximately 6 years
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: