Clinical trial NCT06024174: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: BMS-986466
KRAS G12C-mutant
Pancreatic duct adenocarcinoma
Biliary tract cancer
Colorectal cancer
Non-small cell lung cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2023-09-06
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Number of participants with dose limiting toxicity (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to approximately 2 years
measure: Number of participants with AEs leading to discontinuation
timeFrame: Up to approximately 2 years
measure: Number of participants with deaths
timeFrame: Up to approximately 2 years
measure: Overall response rate (ORR) assessed by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to approximately 60 days
measure: Time to maximum concentration (Tmax)
timeFrame: Up to approximately 60 days
measure: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUC[0-T])
timeFrame: Up to approximately 60 days
measure: Progression-free survival (PFS) assessed by BICR as per RECIST v1.1
timeFrame: Up to approximately 4 years
measure: Disease Control Rate (DCR) assessed by BICR as per RECIST v1.1
timeFrame: Up to approximately 4 years
measure: Duration of Response (DOR) assessed by BICR as per RECIST v1.1
timeFrame: Up to approximately 4 years
measure: Time to response (TTR)
timeFrame: Up to approximately 4 years
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2 years
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to approximately 2 years
measure: Number of participants with AEs leading to discontinuation
timeFrame: Up to approximately 2 years
measure: Number of participants with deaths
timeFrame: Up to approximately 2 years
measure: Pharmacodynamic (PD) profile as measured by phosphorylation of extracellular signal-regulated kinase (pERK) levels in blood
timeFrame: Up to approximately 30 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0047
state: California
city: Athens
country: United States
facility: Local Institution - 0040
state: Georgia
city: Hackensack
country: United States
facility: Local Institution - 0025
state: New Jersey
city: Morristown
country: United States
facility: Local Institution - 0008
state: New Jersey
city: Westmead
country: Australia
facility: Local Institution - 0053
state: New South Wales
city: Helsinki
country: Finland
facility: Local Institution - 0083
city: Lille
country: France
facility: Local Institution - 0020
city: Petah Tikva
country: Israel
facility: Local Institution - 0082
state: HaMerkaz
city: Tel Aviv
country: Israel
facility: Local Institution - 0081
state: Tell Abīb
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: