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 Details
Study Description
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).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part 1: DDI Cohort
|
Drug: BMS-986466
Specified dose on specified days
Other Names:
Drug: Adagrasib
Specified dose on specified days
Other Names:
|
Experimental: Part 1: Dose Escalation
|
Drug: BMS-986466
Specified dose on specified days
Other Names:
Drug: Adagrasib
Specified dose on specified days
Other Names:
Drug: Cetuximab
Specified dose on specified days
Other Names:
|
Experimental: Part 2: Dose Expansion
|
Drug: BMS-986466
Specified dose on specified days
Other Names:
Drug: Adagrasib
Specified dose on specified days
Other Names:
Drug: Cetuximab
Specified dose on specified days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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) [Up to approximately 2 years]
Part 2 only
- Number of participants with serious adverse events (SAEs) [Up to approximately 2 years]
Part 2 only
- 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
- Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood [Up to approximately 30 days]
Eligibility Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294-3300 |
2 | Valkyrie Clinical Trials | Los Angeles | California | United States | 90067 |
3 | University Cancer & Blood Center, LLC | Athens | Georgia | United States | 30607 |
4 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
5 | Atlantic Health System Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
6 | Local Institution - 0075 | Ciudad Autónoma de Buenos Aires | Buenos Aires | Argentina | C1426ANZ |
7 | Local Institution - 0084 | ABB | Ciudad Autónoma De Buenos Aires | Argentina | C1199ABB |
8 | Local Institution - 0076 | Buenos Aires | Argentina | 1431 | |
9 | Local Institution - 0077 | Córdoba | Argentina | X5000HWE | |
10 | Local Institution - 0078 | Elizabeth Vale | South Australia | Australia | 5112 |
11 | Local Institution - 0049 | Brussels | Bruxelles-Capitale, Région De | Belgium | 1200 |
12 | Local Institution - 0048 | Gent | Oost-Vlaanderen | Belgium | 9000 |
13 | Local Institution - 0050 | Leuven | Vlaams-Brabant | Belgium | 3000 |
14 | Local Institution - 0020 | Lille | France | 59037 | |
15 | Local Institution - 0082 | Petah Tikva | HaMerkaz | Israel | 4941492 |
16 | Local Institution - 0081 | Tel Aviv | Tell Abīb | Israel | 6423906 |
17 | Local Institution - 0043 | Ravenna | Emilia-Romagna | Italy | 48121 |
18 | Local Institution - 0042 | Milan | Milano | Italy | 20162 |
19 | Local Institution - 0046 | Rome | Roma | Italy | 00144 |
20 | Local Institution - 0065 | Badalona | Barcelona [Barcelona] | Spain | 08916 |
21 | Local Institution - 0069 | Barcelona | Barcelona [Barcelona] | Spain | 08035 |
22 | Local Institution - 0066 | Madrid | Madrid, Comunidad De | Spain | 28009 |
23 | Local Institution - 0070 | Madrid | Madrid, Comunidad De | Spain | 28034 |
24 | Local Institution - 0067 | Madrid | Madrid, Comunidad De | Spain | 28041 |
25 | Local Institution - 0068 | Sevilla | Spain | 41013 |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- BMS Clinical Trial Information
- FDA Safety Alerts and Recalls
- BMS Clinical Trial Patient Recruiting
- Investigator Inquiry Form
Publications
None provided.- CA126-0015
- 2023-505070-15