Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2, Open-Label, Dose-Escalation, Dose-Enrichment, and Dose-Expansion Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BLU-924 (SAR449336) as Monotherapy and Combination Therapy in Participants With Advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer Harboring KRAS Mutations

NCT ID: NCT07629960Sponsor: Blueprint Medicines CorporationLast updated: 2026-06-05

Summary

A first in human study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of BLU-924 / SAR449336, a pan-KRAS inhibitor, in participants with advanced Pancreatic Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer harboring KRAS mutations.

Detailed description

This is an open-label, multi-center, Phase 1/2 study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of BLU-924, a pan-KRAS inhibitor, in participants with metastatic KRAS mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC). The monotherapy part of the study includes Dose Escalation, Dose Enrichment, and Dose Expansion. Participants enrolled during Dose Escalation and Dose Enrichment will be evaluated for dose limiting toxicities (DLTs) to determine the MTD. Participants enrolled into disease-specific Enrichment cohorts will enable a more robust characterization of safety, PK, pharmacodynamics, and preliminary clinical activity. Enrolment into Dose Expansion will follow the identification of at least 1 recommended dose for expansion (RDFE) based on data from the Dose Escalation and Dose Enrichment. No combination arm is active at this time.

Arms & interventions

  • DrugBLU-924

    Tablet

Outcome measures

Primary

  • Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs)

    Any of the prespecified AEs that are attributable to the study treatment, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes.

    Time frame: Up to 5 years

  • Dose Escalation, Enrichment and Expansion: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs

    An adverse event (AE) is any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it.

    Time frame: Up to 5 years

  • Dose Escalation and Enrichment: Maximum Tolerated Dose (MTD) of BLU-924

    Time frame: Up to 5 years

  • Dose Escalation and Enrichment: Recommended Dose for Expansion (RDFE) of BLU-924

    Time frame: Up to 5 years

  • Dose Expansion: Overall Response Rate (ORR)

    Time frame: Up to 5 years

Secondary

  • Dose Escalation and Enrichment: Overall Response Rate (ORR)

    Time frame: Up to 5 years

  • Dose Escalation, Enrichment, and Expansion: Duration of Response (DOR)

    Time frame: Up to 5 years

  • Dose Escalation, Enrichment, and Expansion: Disease Control Rate (DCR)

    Time frame: Up to 5 years

  • Dose Escalation, Enrichment and Expansion: Progression-free Survival (PFS)

    Time frame: Up to 5 years

  • Dose Expansion: Overall Survival (OS)

    Time frame: Up to 5 years

  • Dose Escalation, Enrichment and Expansion: AUC - Area Under the Plasma Concentration Time Curve for BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: Cmax - Maximum Plasma Concentration for BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: Cmin - Minimum Plasma Concentration of BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: Tmax - Time to Maximum Plasma Drug Concentration for BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: t1/2 - Terminal Half-life of BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: CL/F - Apparent Oral Clearance of BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: Vc/F- Apparent Volume of Central Compartment of BLU-924

    Time frame: Up to 2 years

  • Dose Escalation, Enrichment and Expansion: Vd- Volume of Distribution of BLU-924

    Time frame: Up to 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. Pathologically confirmed diagnosis of metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) with evidence of a single KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA). 2. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. 4. Patients must have received all standard therapies for their cancer type in the metastatic setting, unless they are unable to receive such therapies due to clinical characteristics, comorbidities, or other medically justified reasons. Exclusion Criteria: 1. History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol. 2. Active brain metastases (participants with asymptomatic brain metastases may be eligible). 3. Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders. 4. Active or uncontrolled systemic infection, such as tuberculosis, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study locations (1)

Next Oncology Virginia Cancer Specialist

Fairfax, Virginia, 22031

Recruiting
A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations | Cancerify