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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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT06024174
Collaborator
(none)
410
Enrollment
25
Locations
3
Arms
70.6
Anticipated Duration (Months)
16.4
Patients Per Site
0.2
Patients Per Site Per Month

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

Study Type:
Interventional
Anticipated Enrollment :
410 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Sep 6, 2023
Anticipated Primary Completion Date :
Aug 5, 2027
Anticipated Study Completion Date :
Jul 25, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: DDI Cohort

Drug: BMS-986466
Specified dose on specified days
Other Names:
  • BBP-398
  • IACS-15509

    • Drug: Adagrasib
    Specified dose on specified days
    Other Names:
  • MRTX849
  • KRAZATI®

    		•
    Experimental: Part 1: Dose Escalation

    Drug: BMS-986466
    Specified dose on specified days
    Other Names:
  • BBP-398
  • IACS-15509

    • Drug: Adagrasib
    Specified dose on specified days
    Other Names:
  • MRTX849
  • KRAZATI®

    • Drug: Cetuximab
    Specified dose on specified days
    Other Names:
  • Erbitux®

    		•
    Experimental: Part 2: Dose Expansion

    Drug: BMS-986466
    Specified dose on specified days
    Other Names:
  • BBP-398
  • IACS-15509

    • Drug: Adagrasib
    Specified dose on specified days
    Other Names:
  • MRTX849
  • KRAZATI®

    • Drug: Cetuximab
    Specified dose on specified days
    Other Names:
  • Erbitux®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants with dose limiting toxicity (DLTs) [Up to 28 days]

    2. Number of participants with adverse events (AEs) [Up to approximately 2 years]

    3. Number of participants with serious adverse events (SAEs) [Up to approximately 2 years]

    4. Number of participants with AEs leading to discontinuation [Up to approximately 2 years]

    5. Number of participants with deaths [Up to approximately 2 years]

    6. 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

    1. Maximum observed plasma concentration (Cmax) [Up to approximately 60 days]

    2. Time to maximum concentration (Tmax) [Up to approximately 60 days]

    3. 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]

    4. Progression-free survival (PFS) assessed by BICR as per RECIST v1.1 [Up to approximately 4 years]

    5. Disease Control Rate (DCR) assessed by BICR as per RECIST v1.1 [Up to approximately 4 years]

    6. Duration of Response (DOR) assessed by BICR as per RECIST v1.1 [Up to approximately 4 years]

    7. Time to response (TTR) [Up to approximately 4 years]

    8. Number of participants with adverse events (AEs) [Up to approximately 2 years]

      Part 2 only

    9. Number of participants with serious adverse events (SAEs) [Up to approximately 2 years]

      Part 2 only

    10. Number of participants with AEs leading to discontinuation [Up to approximately 2 years]

      Part 2 only

    11. Number of participants with deaths [Up to approximately 2 years]

      Part 2 only

    12. Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood [Up to approximately 30 days]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT06024174
    Other Study ID Numbers:
    • CA126-0015
    • 2023-505070-15
    First Posted:
    Sep 6, 2023
    Last Update Posted:
    Sep 6, 2023
    Last Verified:
    Aug 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bristol-Myers Squibb
    BMS-986466
    KRAS G12C-mutant
    Pancreatic duct adenocarcinoma
    Biliary tract cancer
    Colorectal cancer
    Non-small cell lung cancer
    Additional relevant MeSH terms:
    Neoplasms
    Cetuximab
    Adagrasib

    Study Results

    No Results Posted as of Sep 6, 2023