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

Study Overview
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Brief Summary
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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).

Official Title
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Phase 1/2 Open-label Study of BMS-986466 in Combination With Adagrasib With or Without Cetuximab in Participants With KRAS G12C-mutant Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: BMS-986466
* Drug: Adagrasib
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Key Inclusion Criteria: 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. Key Exclusion Criteria: 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 Note: Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: DDI Cohort<br> | Drug: BMS-986466<br>* Specified dose on specified days<br>* Other names: IACS-15509;Drug: Adagrasib<br>* Specified dose on specified days<br>* Other names: KRAZATI®;|
| Experimental: Part 1: Dose Escalation<br> | Drug: BMS-986466<br>* Specified dose on specified days<br>* Other names: IACS-15509;Drug: Adagrasib<br>* Specified dose on specified days<br>* Other names: KRAZATI®;Drug: Cetuximab<br>* Specified dose on specified days<br>* Other names: Erbitux®;|
| Experimental: Part 2: Dose Expansion<br> | Drug: BMS-986466<br>* Specified dose on specified days<br>* Other names: IACS-15509;Drug: Adagrasib<br>* Specified dose on specified days<br>* Other names: KRAZATI®;Drug: Cetuximab<br>* Specified dose on specified days<br>* Other names: Erbitux®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicity (DLTs) |  | Up to 28 days | 
| Number of participants with adverse events (AEs) |  | Up to approximately 2 years | 
| Number of participants with serious adverse events (SAEs) |  | Up to approximately 2 years | 
| Number of participants with AEs leading to discontinuation |  | Up to approximately 2 years | 
| Number of participants with deaths |  | Up to approximately 2 years | 
| Overall response rate (ORR) assessed by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) |  | Up to approximately 60 days | 
| Time to maximum concentration (Tmax) |  | Up to approximately 60 days | 
| Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUC[0-T]) |  | Up to approximately 60 days | 
| Progression-free survival (PFS) assessed by BICR as per RECIST v1.1 |  | Up to approximately 4 years | 
| Disease Control Rate (DCR) assessed by BICR as per RECIST v1.1 |  | Up to approximately 4 years | 
| Duration of Response (DOR) assessed by BICR as per RECIST v1.1 |  | Up to approximately 4 years | 
| Time to response (TTR) |  | Up to approximately 4 years | 
| Number of participants with adverse events (AEs) | Part 2 only | Up to approximately 2 years | 
| Number of participants with serious adverse events (SAEs) | Part 2 only | Up to approximately 2 years | 
| Number of participants with AEs leading to discontinuation | Part 2 only | Up to approximately 2 years | 
| Number of participants with deaths | Part 2 only | Up to approximately 2 years | 
| Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood |  | Up to approximately 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMS-986466, KRAS G12C-mutant, Pancreatic duct adenocarcinoma, Biliary tract cancer, Colorectal cancer, Non-small cell lung cancer