NCT06024174 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2025-07-22

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)

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outcome · POSTED

Part 1: Number of Participants With Adverse Events (AEs)

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outcome · POSTED

Part 1: Number of Participants With Serious Adverse Events (SAEs)

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outcome · POSTED

Part 1: Number of Participants With AEs Leading to Discontinuation

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outcome · POSTED

Part 1: Number of Participants Who Died

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outcome · POSTED

Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

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outcome · POSTED

Part 1: Maximum Observed Plasma Concentration (Cmax)

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outcome · POSTED

Part 1: Time to Maximum Concentration (Tmax)

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outcome · POSTED

Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])

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outcome · POSTED

Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1

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outcome · POSTED

Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1

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outcome · POSTED

Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1

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outcome · POSTED

Part 2- Time to Response (TTR)

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outcome · POSTED

Part 2- Number of Participants With Adverse Events (AEs)

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outcome · POSTED

Part 2- Number of Participants With Serious Adverse Events (SAEs)

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outcome · POSTED

Part 2- Number of Participants With AEs Leading to Discontinuation

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outcome · POSTED

Part 2- Number of Participants Who Died

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outcome · POSTED

Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: BMS-986466
Drug: Adagrasib
label
Part 1: DDI Cohort
type
EXPERIMENTAL
intervention Names
Drug: BMS-986466
Drug: Adagrasib
Drug: Cetuximab
label
Part 1: Dose Escalation
type
EXPERIMENTAL
intervention Names
Drug: BMS-986466
Drug: Adagrasib
Drug: Cetuximab
label
Part 2: Dose Expansion
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1: DDI Cohort
Part 1: Dose Escalation
Part 2: Dose Expansion
description
Specified dose on specified days
name
BMS-986466
other Names
BBP-398
IACS-15509
type
DRUG
arm Group Labels
Part 1: DDI Cohort
Part 1: Dose Escalation
Part 2: Dose Expansion
description
Specified dose on specified days
name
Adagrasib
other Names
MRTX849
KRAZATI®
type
DRUG
arm Group Labels
Part 1: Dose Escalation
Part 2: Dose Expansion
description
Specified dose on specified days
name
Cetuximab
other Names
Erbitux®
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 5
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days * Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \\\> 3 Ã- ULN and concurrent increase in total bilirubin \\\> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee
measure
Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)
time Frame
Cycle 1 (Each cycle consist of 28 days)
description
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
measure
Part 1: Number of Participants With Adverse Events (AEs)
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.
measure
Part 1: Number of Participants With Serious Adverse Events (SAEs)
time Frame
From first dose until 30 days after last dose (Up to approximately 3 months)
description
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen
measure
Part 1: Number of Participants With AEs Leading to Discontinuation
time Frame
From first dose until 30 days after last dose (Up to approximately 3 months)
description
Death due to any cause was assessed.
measure
Part 1: Number of Participants Who Died
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure
Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)

secondary Outcomes

description
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
measure
Part 1: Maximum Observed Plasma Concentration (Cmax)
time Frame
Cycle 1 Day 1 (Each cycle consist of 28 days)
description
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
measure
Part 1: Time to Maximum Concentration (Tmax)
time Frame
Cycle 1 Day 1 (Each cycle consist of 28 days)
description
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
measure
Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])
time Frame
Cycle 1 Day 1 (Each cycle consist of 28 days)
description
Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on Investigator assessments (per RECIST v1.1), or death due to any cause, whichever occurs first Calculated using Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure
Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
description
Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants.
measure
Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
description
Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per BICR assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
measure
Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
description
Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per BICR. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
measure
Part 2- Time to Response (TTR)
time Frame
From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
description
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
measure
Part 2- Number of Participants With Adverse Events (AEs)
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.
measure
Part 2- Number of Participants With Serious Adverse Events (SAEs)
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
measure
Part 2- Number of Participants With AEs Leading to Discontinuation
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
Death due to any cause was assessed.
measure
Part 2- Number of Participants Who Died
time Frame
From first dose until 100 days after last dose (Up to approximately 5 months)
description
Blood samples were collected for assessing pharmacodynamic parameters.
measure
Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker
time Frame
Baseline and Cycle 1 Day 1 (Each cycle consist of 28 days)

Full 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).

Source references