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RecruitingNCT07629960Updated Sep 21, 2026

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

A Phase 1/2 interventional study of BLU-924 in Advanced Solid Tumor, Non-Small Cell Lung Cancer and Colorectal Neoplasms, sponsored by Blueprint Medicines Corporation. Recruiting at 16 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Blueprint Medicines Corporation · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
265
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Advanced Solid Tumor
  • Non-Small Cell Lung Cancer
  • Colorectal Neoplasms
  • Pancreatic Ductal Adenocarcinoma

Keywords

  • Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation
  • Metastatic Non-Small Lung Cell Cancer
  • Metastatic Colorectal Cancer (CRC)
  • Metastatic Pancreatic Ductal Adenocarcinoma
  • KRAS G12A
  • KRAS G12C
  • KRAS G12D
  • KRAS G12S
  • KRAS G12V
  • Solid Tumor, Adult
  • KRAS-mutant
  • KRAS-positive
  • KRAS G13D
  • Pan-KRAS inhibitor
  • KRAS inhibitor
  • First-in-human
  • Solid tumor
  • Advanced cancer
  • Adult solid tumor
  • Metastatic solid tumor
  • Colorectal cancer
  • Colon cancer
  • Rectal cancer
  • Metastatic colorectal cancer
  • Pancreatic cancer
  • Pancreatic ductal adenocarcinoma
  • PDAC
  • Metastatic pancreatic cancer
  • Lung cancer
  • NSCLC
  • Precision oncology
  • Targeted therapy
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy 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

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.

04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
265 participants (estimated)

Study arms

  • Experimental
    Monotherapy Part: BLU-924 Dose Escalation, Dose Enrichment, and Dose Expansion

    Participants will receive BLU-924 oral tablet, once daily as monotherapy during Dose Escalation followed by Dose Enrichment. During Dose Enrichment, participants with PDAC, NSCLC or CRC will receive BLU-924 at selected dose levels below the current escalation dose or, if Dose Escalation is complete, below the MTD. During Dose Expansion, participants will receive RDFE of BLU-924 oral tablet, once daily as monotherapy determined during escalation monotherapy part. Dose Expansion may be initiated to further assess the safety, antitumor activity, PK, and pharmacodynamics of BLU-924 at RDFE in indication-specific cohorts (PDAC, NSCLC, or CRC) harboring a KRAS mutation.

    Drug: BLU-924

Interventions

  • DrugBLU-924

    Tablet

    Also known as: SAR449336

05

What researchers measure

Primary outcomes

  1. 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

  2. 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

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

    Time frame: Up to 5 years

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

    Time frame: Up to 5 years

  5. Dose Expansion: Overall Response Rate (ORR)

    Time frame: Up to 5 years

Secondary outcomes

  1. Dose Escalation and Enrichment: Overall Response Rate (ORR)

    Time frame: Up to 5 years

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

    Time frame: Up to 5 years

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

    Time frame: Up to 5 years

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

    Time frame: Up to 5 years

  5. Dose Expansion: Overall Survival (OS)

    Time frame: Up to 5 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

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

    Time frame: Up to 2 years

06

Study locations

3 of 16 sites recruiting
  • Florida Cancer Specialists & Research Institute - Sarasota
    Sarasota, Florida 34242, United States
    Recruiting
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
    Recruiting
  • Mary Bird Perkins Cancer Center
    Baton Rouge, Louisiana 70809, United States
    Not yet recruiting
  • Massachusetts General Hospital - Main Campus
    Boston, Massachusetts 02114, United States
    Not yet recruiting
  • University of Michigan Medical School Rogel Cancer Center
    Ann Arbor, Michigan 48109-5843, United States
    Not yet recruiting
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601-2191, United States
    Not yet recruiting
  • NYU Langone Health Perlmutter Cancer Center
    New York, New York 10016, United States
    Not yet recruiting
  • Tennessee Oncology, PLLC
    Nashville, Tennessee 37203, United States
    Not yet recruiting
  • The University of Texas MD Anderson Cancer Center - Texas Medical Center
    Houston, Texas 77030, United States
    Not yet recruiting
  • Next Oncology Virginia Cancer Specialist
    Fairfax, Virginia 22031, United States
    Recruiting
  • Mi Cancer Center Barcelona (Pratia Sirius Barcelona)
    Barcelona, Catalonia 08017, Spain
    Not yet recruiting
  • Hospital Universitario Vall d'Hebron
    Barcelona, Catalonia 08035, Spain
    Not yet recruiting
  • Hospital General Universitrio Gregorio Maranon
    Madrid, Madrid 28007, Spain
    Not yet recruiting
  • Hospital Universitario 12 de Octubre
    Madrid, Madrid 28009, Spain
    Not yet recruiting
  • NEXT Oncology - Madrid
    Pozuelo de Alarcón, Madrid 28223, Spain
    Not yet recruiting
  • Clinica Universidad de Navarra (CUN)
    Pamplona, Navarre 31008, Spain
    Not yet recruiting
07

References and documents

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07629960
Lead sponsor
Blueprint Medicines Corporation
Collaborators
Sanofi
Responsible party
Sponsor
First posted
Jun 5, 2026
Start date
Jun 4, 2026
Primary completion
Sep 2029 (estimated)
Completion
Jul 2031 (estimated)
Last update
Sep 21, 2026

Study contacts

Blueprint Medicines
Contact
medinfo@blueprintmedicines.com
1-888-258-7768

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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