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

Bristol-Myers Squibb (BMS)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Advanced Solid Tumors

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06024174

CA126-0015

2023-505070-15 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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5 participants in 3 patient groups

Part 1: DDI Cohort

Experimental group

Treatment:

Drug: BMS-986466

Drug: Adagrasib

Part 1: Dose Escalation

Experimental group

Treatment:

Drug: Cetuximab

Drug: BMS-986466

Drug: Adagrasib

Part 2: Dose Expansion

Experimental group

Treatment:

Drug: Cetuximab

Drug: BMS-986466

Drug: Adagrasib