A Clinical Study of MK-1084 With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)

Merck Sharp & Dohme (MSD)

Status and phase: Begins enrollment this month; Phase 3

Conditions: Rectal Adenocarcinoma; Colon Adenocarcinoma

Treatments: Drug: Oxaliplatin; Drug: MK-1084; Drug: Bevacizumab; Drug: Leucovorin/levofolinate calcium; Biological: Cetuximab; Drug: 5-Fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT06997497

1084-012

MK-1084-012 (Other Identifier)

KANDLELIT-012 (Other Identifier)

Details and patient eligibility

About

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.

Full description

This study will have 2 parts.

Enrollment: 477 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

477 participants in 2 patient groups

MK-1084 + Cetuximab + mFOLFOX6

Experimental group

Description:

Participants will receive MK-1084 orally once daily (QD), cetuximab per label every 2 weeks (Q2W), and mFOLFOX6 chemotherapy: oxaliplatin per label every 2 weeks (Q2W), leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Treatment will continue until criteria for discontinuation is met.

Treatment:

Biological: Cetuximab

Drug: 5-Fluorouracil

Drug: Leucovorin/levofolinate calcium

Drug: MK-1084

Drug: Oxaliplatin

mFOLFOX6

Active Comparator group

Description:

Participants will receive mFOLFOX6 chemotherapy: oxaliplatin per label Q2W, leucovorin or levofolinate calcium per label Q2W, and 5-fluorouracil (5-FU) per label Q2W. Participants may also receive bevacizumab Q2W at the investigator's discretion. Treatment will continue until criteria for discontinuation is met.

Treatment:

Drug: 5-Fluorouracil

Drug: Leucovorin/levofolinate calcium

Drug: Bevacizumab

Drug: Oxaliplatin