A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors

NCT06024174 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA126-00152023-505070-15
• Study Type: interventional
• Target: 5
• Locations: 5 countries
• Sites: 9

Brief Summary

The purpose of this study is to find a safe, tolerable, and efficacious dose of BMS-986466 when given orally, in combination with adagrasib with or without cetuximab in participants with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), pancreatic duct adenocarcinoma (PDAC), biliary tract cancer (BTC), or colorectal cancer (CRC).

Conditions

Advanced Solid Tumors

Keywords

BMS-986466; KRAS G12C-mutant; Pancreatic duct adenocarcinoma; Biliary tract cancer; Colorectal cancer; Non-small cell lung cancer

Outcome Measures

Primary Outcomes (6)

• Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)

  A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days * Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \\\> 3 Ã- ULN and concurrent increase in total bilirubin \\\> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

  Cycle 1 (Each cycle consist of 28 days)

• Part 1: Number of Participants With Adverse Events (AEs)

  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

  From first dose until 100 days after last dose (Up to approximately 5 months)

• Part 1: Number of Participants With Serious Adverse Events (SAEs)

  A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.

  From first dose until 30 days after last dose (Up to approximately 3 months)

• Part 1: Number of Participants With AEs Leading to Discontinuation

  An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen

  From first dose until 30 days after last dose (Up to approximately 3 months)

• Part 1: Number of Participants Who Died

  Death due to any cause was assessed.

  From first dose until 100 days after last dose (Up to approximately 5 months)

• Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)

Secondary Outcomes (12)

• Part 1: Maximum Observed Plasma Concentration (Cmax)

  Cycle 1 Day 1 (Each cycle consist of 28 days)

• Part 1: Time to Maximum Concentration (Tmax)

  Cycle 1 Day 1 (Each cycle consist of 28 days)

• Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])

  Cycle 1 Day 1 (Each cycle consist of 28 days)

• Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1

  From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)

• Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1

  From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)

Study Arms (3)

Part 1: DDI Cohort

EXPERIMENTAL

Drug: BMS-986466; Drug: Adagrasib

Part 1: Dose Escalation

EXPERIMENTAL

Drug: BMS-986466; Drug: Adagrasib; Drug: Cetuximab

Part 2: Dose Expansion

EXPERIMENTAL

Drug: BMS-986466; Drug: Adagrasib; Drug: Cetuximab

Interventions

BMS-986466 DRUG

Specified dose on specified days

Also known as: BBP-398, IACS-15509

Part 1: DDI Cohort; Part 1: Dose Escalation; Part 2: Dose Expansion

Adagrasib DRUG

Specified dose on specified days

Also known as: MRTX849, KRAZATI®

Part 1: DDI Cohort; Part 1: Dose Escalation; Part 2: Dose Expansion

Cetuximab DRUG

Specified dose on specified days

Also known as: Erbitux®

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1:
• Individuals with a confirmed diagnosis of advanced KRAS G12C mutant NSCLC, CRC, PDAC and BTC that has spread to other parts of the body and cannot be removed surgically, may or may not have received previous treatment with KRAS G12C inhibitors.
• For NSCLC and CRC: Individuals must have a documented KRAS G12C mutation status from NYS or FDA approved/cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample collected at the time of screening.
• 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.
• Are relapsed or refractory to available standard of care treatments.
• Part 2:
• 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.
• Individuals must have a documented KRAS G12C mutation from FDA or NYS approved/ cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample and /or tumor samples collected at the time of screening or from archival biopsies (less than 1 year old).
• Have failed or disease recurrence or are not able to tolerate after at least 1 pervious line of therapy.

You may not qualify if:

• Have tumors with known BARF V600X, PTPN11 or KRASQ61X mutations.
• Have or any significant heart disease or condition.
• Receiving any medications that are substrate of CYP3A4 or inducers and/ or inhibitors

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (9)

Local Institution - 0047

Los Angeles, California, 90067, United States

Location

Local Institution - 0040

Athens, Georgia, 30607, United States

Location

Local Institution - 0025

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 0008

Morristown, New Jersey, 07960, United States

Location

Local Institution - 0053

Westmead, New South Wales, 2145, Australia

Location

Local Institution - 0083

Helsinki, 00029, Finland

Location

Local Institution - 0020

Lille, 59037, France

Location

Local Institution - 0082

Petah Tikva, Central District, 4941492, Israel

Location

Local Institution - 0081

Tel Aviv, Tell Abīb, 6423906, Israel

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Biliary Tract Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

adagrasib; Cetuximab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2023
• First Posted: September 6, 2023
• Study Start: November 9, 2023
• Primary Completion: May 13, 2024
• Study Completion: May 13, 2024
• Last Updated: July 22, 2025
• Results First Posted: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

AU (1); US (4); FI (1); IL (2); FR (1)