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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06024174
• Other study ID #: CA126-0015
• Secondary ID: 2023-505070-15
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 9, 2023
• Est. completion date: May 14, 2024

Study information

• Verified date: March 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 410
• Est. completion date: May 14, 2024
• Est. primary completion date: May 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• BMS-986466
Specified dose on specified days
• Adagrasib
Specified dose on specified days
• Cetuximab
Specified dose on specified days

Locations

Country	Name	City	State
Argentina	Local Institution - 0084	ABB	Ciudad Autónoma De Buenos Aires
Argentina	Local Institution - 0076	Buenos Aires
Argentina	Local Institution - 0075	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Local Institution - 0077	Córdoba
Argentina	Local Institution - 0086	Córdoba
Australia	Local Institution - 0078	Elizabeth Vale	South Australia
Australia	Local Institution - 0053	Westmead	New South Wales
Belgium	Local Institution - 0049	Brussels	Bruxelles-Capitale, Région De
Belgium	Local Institution - 0048	Gent	Oost-Vlaanderen
Belgium	Local Institution - 0050	Leuven	Vlaams-Brabant
France	CHU de Bordeaux Hop St ANDRE	Bordeaux	Aquitaine
France	Hopital Claude Huriez - CHU de Lille	Lille
France	Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone	Marseille	Bouches-du-Rhône
France	Centre Hospitalier Universitaire de Poitiers	Poitiers	Vienne
France	Gustave Roussy	Villejuif	Val-de-Marne
Israel	Local Institution - 0082	Petah Tikva	HaMerkaz
Israel	Local Institution - 0081	Tel Aviv	Tell Abib
Italy	Local Institution - 0042	Milan	Milano
Italy	Local Institution - 0043	Ravenna	Emilia-Romagna
Italy	Local Institution - 0046	Rome	Roma
Spain	Local Institution - 0065	Badalona	Barcelona [Barcelona]
Spain	Local Institution - 0069	Barcelona	Barcelona [Barcelona]
Spain	Local Institution - 0066	Madrid	Madrid, Comunidad De
Spain	Local Institution - 0067	Madrid	Madrid, Comunidad De
Spain	Local Institution - 0070	Madrid	Madrid, Comunidad De
Spain	Local Institution - 0068	Sevilla
United States	University Cancer Blood Ctr	Athens	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Atlantic Health System Morristown Medical Center	Morristown	New Jersey
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  France,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicity (DLTs)		Up to 28 days
Primary	Number of participants with adverse events (AEs)		Up to approximately 2 years
Primary	Number of participants with serious adverse events (SAEs)		Up to approximately 2 years
Primary	Number of participants with AEs leading to discontinuation		Up to approximately 2 years
Primary	Number of participants with deaths		Up to approximately 2 years
Primary	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	Maximum observed plasma concentration (Cmax)		Up to approximately 60 days
Secondary	Time to maximum concentration (Tmax)		Up to approximately 60 days
Secondary	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
Secondary	Progression-free survival (PFS) assessed by BICR as per RECIST v1.1		Up to approximately 4 years
Secondary	Disease Control Rate (DCR) assessed by BICR as per RECIST v1.1		Up to approximately 4 years
Secondary	Duration of Response (DOR) assessed by BICR as per RECIST v1.1		Up to approximately 4 years
Secondary	Time to response (TTR)		Up to approximately 4 years
Secondary	Number of participants with adverse events (AEs)	Part 2 only	Up to approximately 2 years
Secondary	Number of participants with serious adverse events (SAEs)	Part 2 only	Up to approximately 2 years
Secondary	Number of participants with AEs leading to discontinuation	Part 2 only	Up to approximately 2 years
Secondary	Number of participants with deaths	Part 2 only	Up to approximately 2 years
Secondary	Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood		Up to approximately 30 days

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls