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
Phase 1
Terminated
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT06024174
- Lead Sponsor
- Bristol-Myers Squibb
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: DDI Cohort BMS-986466 - Part 1: Dose Escalation BMS-986466 - Part 2: Dose Expansion BMS-986466 - Part 1: Dose Escalation Cetuximab - Part 2: Dose Expansion Cetuximab - Part 1: DDI Cohort Adagrasib - Part 1: Dose Escalation Adagrasib - Part 2: Dose Expansion Adagrasib -
- Primary Outcome Measures
Name Time Method 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 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 Number of participants with serious adverse events (SAEs) Up to approximately 2 years
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) Up to approximately 2 years Part 2 only
Number of participants with serious adverse events (SAEs) Up to approximately 2 years Part 2 only
Time to maximum concentration (Tmax) Up to approximately 60 days Duration of Response (DOR) assessed by BICR as per RECIST v1.1 Up to approximately 4 years 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 Maximum observed plasma concentration (Cmax) Up to approximately 60 days Time to response (TTR) Up to approximately 4 years Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood Up to approximately 30 days Number of participants with AEs leading to discontinuation Up to approximately 2 years Part 2 only
Number of participants with deaths Up to approximately 2 years Part 2 only
Trial Locations
- Locations (9)
Local Institution - 0025
🇺🇸Hackensack, New Jersey, United States
Local Institution - 0047
🇺🇸Los Angeles, California, United States
Local Institution - 0053
🇦🇺Westmead, New South Wales, Australia
Local Institution - 0020
🇫🇷Lille, France
Local Institution - 0081
🇮🇱Tel Aviv, Tell Abīb, Israel
Local Institution - 0040
🇺🇸Athens, Georgia, United States
Local Institution - 0083
🇫🇮Helsinki, Finland
Local Institution - 0082
🇮🇱Petah Tikva, HaMerkaz, Israel
Local Institution - 0008
🇺🇸Morristown, New Jersey, United States