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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

Terminated Phase 1, PHASE2 Results posted Last updated 22 July 2025
What this trial tests

Phase 1, PHASE2 trial testing BMS-986466 in Advanced Solid Tumors in 5 participants. Terminated before completion.

Timeline
9 November 2023
Primary endpoint
13 May 2024
13 May 2024

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment5
Start date9 November 2023
Primary completion13 May 2024
Estimated completion13 May 2024
Sites9 locations across France, Finland, Israel, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Part 1: Number of Participants With Dose Limiting Toxicity (DLTs) Primary · Cycle 1 (Each cycle consist of 28 days)

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 incr

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID0
Part 1: Number of Participants With Adverse Events (AEs) Primary · From first dose until 100 days after last dose (Up to approximately 5 months)

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.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID4
Part 1: Number of Participants With Serious Adverse Events (SAEs) Primary · From first dose until 30 days after last dose (Up to approximately 3 months)

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.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID1
Part 1: Number of Participants With AEs Leading to Discontinuation Primary · From first dose until 30 days after last dose (Up to approximately 3 months)

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

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID0
Part 1: Number of Participants Who Died Primary · From first dose until 100 days after last dose (Up to approximately 5 months)

Death due to any cause was assessed.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID0
Part 1: Maximum Observed Plasma Concentration (Cmax) Secondary · Cycle 1 Day 1 (Each cycle consist of 28 days)

Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BIDNA± NA
Part 1: Time to Maximum Concentration (Tmax) Secondary · Cycle 1 Day 1 (Each cycle consist of 28 days)

Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BIDNA± NA
Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T]) Secondary · Cycle 1 Day 1 (Each cycle consist of 28 days)

Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.

GroupValue95% CI
Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BIDNA± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: All cause mortality, and serious and non-serious adverse events were collected from from first dose until 100 days after last dose (Up to approximately 5 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID
Serious: 1/5 (20%)
Deaths: 0/5

Serious adverse events (1 terms)

ReactionSystemPart 1: Drug-Drug Interact…
PyrexiaGeneral disorders
Other adverse events (16 terms — click to expand)

ReactionSystemPart 1: Drug-Drug Interact…
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Epigastric discomfortGastrointestinal disorders
ProctalgiaGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Amylase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Lipase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
SomnolenceNervous system disorders
HypotensionVascular disorders

Most-reported serious reactions: Pyrexia.

Data from ClinicalTrials.gov NCT06024174 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.
    Casacuberta-Serra S, González-Larreategui Í, Capitán-Leo D, Soucek L. · · 2024 · cited 43× · PMID 39164274 · DOI 10.1038/s41392-024-01907-z
  2. Targeting <i>KRAS</i> G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.
    Ros J, Vaghi C, Baraibar I, Saoudi González N, et al · · 2024 · cited 35× · PMID 38542278 · DOI 10.3390/ijms25063304
  3. Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies.
    Linehan A, O'Reilly M, McDermott R, O'Kane GM. · · 2024 · cited 24× · PMID 38576709 · DOI 10.3389/fmed.2024.1369136
  4. Inhibition of the RAF/MEK/ERK Signaling Cascade in Pancreatic Cancer: Recent Advances and Future Perspectives.
    Adamopoulos C, Cave DD, Papavassiliou AG, Papavassiliou AG. · · 2024 · cited 19× · PMID 38338909 · DOI 10.3390/ijms25031631
  5. Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.
    Zhang F, Wang B, Wu M, Zhang L, et al · · 2025 · cited 9× · PMID 40303413 · DOI 10.3389/fimmu.2025.1509173
  6. Genetic Signature of Human Pancreatic Cancer and Personalized Targeting.
    Reshkin SJ, Cardone RA, Koltai T. · · 2024 · cited 9× · PMID 38607041 · DOI 10.3390/cells13070602
  7. KRAS-Driven Tumorigenesis and KRAS-Driven Therapy in Pancreatic Adenocarcinoma.
    Than MT, O'Hara M, Stanger BZ, Reiss KA. · · 2024 · cited 8× · PMID 39118358 · DOI 10.1158/1535-7163.mct-23-0519
  8. Dual inhibition of HERs and PD-1 counteract resistance in KRAS&lt;sup&gt;G12C&lt;/sup&gt;-mutant head and neck cancer.
    Novoplansky O, Jagadeeshan S, Prasad M, Yegodayev KM, et al · · 2024 · cited 6× · PMID 39567998 · DOI 10.1186/s13046-024-03227-0

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