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

Phase 3RecruitingNCT06997497

Merck Sharp & Dohme LLC477 enrolled

Overview

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.

This study will have 2 parts.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

477

Conditions

Colon Adenocarcinoma Rectal Adenocarcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (83)

Orlando Health Cancer Institute ( Site 0065)

Orlando, Florida, United States

RECRUITING

Norton Cancer Institute, Audubon Hospital Campus ( Site 0054)

Louisville, Kentucky, United States

RECRUITING

Renown Regional Medical Center ( Site 0056)

Reno, Nevada, United States

RECRUITING

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

Hackensack, New Jersey, United States

Outcomes

Primary Outcomes

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

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 Outcomes

Objective Response Rate (ORR)

ORR is defined as a confirmed complete response (CR: the disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR). The percentage of participants who experience CR or PR as assessed by BICR will be presented.

Time frame: Up to approximately 3 years

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 5 years

Duration of Response (DOR)

For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.

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

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented. A higher score indicates a better outcome.