What side effects are associated with this type of intervention?

Treatments for solid tumors, particularly those involving KRAS G12C inhibitors like adagrasib and EGFR inhibitors like cetuximab, commonly cause gastrointestinal issues such as nausea and diarrhea, fatigue, liver enzyme elevations, and skin reactions like acneiform rash. Cetuximab can also cause infusion reactions and hypomagnesemia. Combining these agents may result in overlapping toxicities, especially gastrointestinal and dermatologic side effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of solid tumors, particularly those targeting specific mutations and pathways. Adagrasib, a KRAS G12C inhibitor, is designed to target the KRAS G12C mutation found in various cancers such as non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Cetuximab, an EGFR inhibitor, is approved for the treatment of metastatic colorectal cancer and head and neck cancer. Other notable approvals include sotorasib, another KRAS G12C inhibitor, which has shown efficacy in treating NSCLC with KRAS G12C mutations. These drugs represent significant advancements in targeted cancer therapy, offering new options for patients with specific genetic profiles.

What other types of research exist?

Promising novel alternatives to BMS-986466 in combination with adagrasib and possibly cetuximab for solid tumors include: 1) Other KRAS G12C inhibitors such as sotorasib, which has shown efficacy in KRAS G12C-mutant cancers. 2) Combining KRAS G12C inhibitors with other targeted therapies like MEK inhibitors (e.g., trametinib) or SHP2 inhibitors (e.g., RMC-4630) to overcome resistance mechanisms. 3) Investigating the use of immune checkpoint inhibitors (e.g., pembrolizumab) in combination with KRAS G12C inhibitors to enhance anti-tumor immune response. These alternatives offer potential for improved outcomes in patients with KRAS G12C-mutant solid tumors.

← Back to Search

Other

BMS-986466 + Adagrasib for KRAS-Mutant Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Bristol-Myers Squibb

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For PDAC and BTC: Participants must have a documented KRAS G12Cmutation from NYS or FDA-approved/cleared, or CE-marked test and blood samples will be collected only for retrospective testing.

Individuals with a confirmed diagnosis of advanced KRAS G12C-mutant NSCLC (Part 2A) or CRC (Part 2B) that has spread to other parts of the body and cannot be removed surgically and have not received previous treatment with KRAS inhibitors.

Must not have

Have or any significant heart disease or condition.

Have tumors with known BARF V600X, PTPN11 or KRASQ61X mutations.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new oral drug, BMS-986466, combined with adagrasib and sometimes cetuximab. It targets patients with advanced cancers that have a specific genetic mutation called KRAS G12C. The treatment aims to stop cancer growth by focusing on this genetic change. Adagrasib is a KRAS G12C inhibitor that has shown promising results in treating metastatic colorectal cancer and has FDA approval for KRAS G12C-mutated NSCLC.

Who is the study for?

This trial is for adults with advanced KRAS G12C-mutant solid tumors like lung, pancreatic, biliary tract, or colorectal cancer that's spread and can't be surgically removed. They should have tried at least one therapy before or not tolerated it. They mustn't have certain other mutations or heart conditions and should avoid specific medications.

What is being tested?

The study tests the safety and effectiveness of BMS-986466 taken orally in combination with adagrasib, with or without cetuximab. It aims to determine the best dose for treating various advanced cancers with a specific mutation (KRAS G12C).

What are the potential side effects?

Potential side effects may include reactions related to the immune system due to cetuximab, liver issues from BMS-986466, and gastrointestinal symptoms from adagrasib. The exact side effects will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My cancer has a specific KRAS G12C mutation.

Select...

My advanced cancer has a KRAS G12C mutation and hasn't been treated with KRAS inhibitors.

Select...

My lung or colon cancer has a specific KRAS G12C mutation.

Select...

My condition worsened or returned after one treatment, or I couldn't tolerate the treatment.

Select...

My condition did not improve after standard treatments.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have any significant heart disease or condition.

Select...

My tumor has a specific genetic mutation (BARF V600X, PTPN11, or KRASQ61X).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Number of participants with AEs leading to discontinuation

Number of participants with adverse events (AEs)

Number of participants with deaths

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Part 2: Dose ExpansionExperimental Treatment3 Interventions

Group II: Part 1: Dose EscalationExperimental Treatment3 Interventions

Group III: Part 1: DDI CohortExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Adagrasib

2023

Completed Phase 1

~20

Cetuximab

2011

Completed Phase 3

~2480

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

KRAS G12C inhibitors, such as adagrasib, target the specific KRAS G12C mutation by binding to the mutant protein and inhibiting its activity, thereby blocking downstream signaling that promotes tumor growth. Cetuximab, an EGFR inhibitor, binds to the epidermal growth factor receptor on cancer cells, preventing its activation and subsequent signaling for cell proliferation and survival. Combining these treatments can effectively disrupt multiple pathways critical for cancer cell growth and survival, offering a more robust therapeutic approach for patients with solid tumors harboring these mutations.

Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer.Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells.