Advanced Solid TumorPhase 1/2NCT07629960
A First-in-Human Trial of BLU-924 (SAR449336) in Advanced Solid Tumors Harboring KRAS Mutations
A Phase 1/2 study testing BLU-924 in people with Advanced Solid Tumor and Non-Small Cell Lung Cancer, run by Blueprint Medicines Corporation at 16 sites in 2 countries.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Non-Small Cell Lung Cancer, Colorectal Neoplasms
- What is being tested?
- BLU-924
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 16 sitesin 2 countries
- Study dates
- 4 Jun 2026to Jul 2031
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- 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.
Who cannot join
- History of additional malignancy within the last 2 years, with some exceptions as specified in the protocol.
- Active brain metastases (participants with asymptomatic brain metastases may be eligible).
- Have received prior targeted treatment(s) against KRAS, including pan-KRAS inhibitors, multi-RAS inhibitors, mutant-selective KRAS inhibitors, and RAS or KRAS degraders.
- 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.
Trial locations and contacts
16 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
16 sites in 2 countries
United States10 sites, 10 recruiting
- Not yet recruiting
University of Michigan Medical School Rogel Cancer Center
Ann Arbor, Michigan, 48109-5843
- Not yet recruiting
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
- Not yet recruiting
Massachusetts General Hospital - Main Campus
Boston, Massachusetts, 02114
- Recruiting
Next Oncology Virginia Cancer Specialist
Fairfax, Virginia, 22031
- Not yet recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601-2191
- Not yet recruiting
The University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, 77030
- Not yet recruiting
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
- Not yet recruiting
NYU Langone Health Perlmutter Cancer Center
New York, New York, 10016
- Recruiting
Florida Cancer Specialists & Research Institute - Sarasota
Sarasota, Florida, 34242
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Spain6 sites, 6 recruiting
- Not yet recruiting
Mi Cancer Center Barcelona (Pratia Sirius Barcelona)
Barcelona, Catalonia, 08017
- Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona, Catalonia, 08035
- Not yet recruiting
Hospital General Universitrio Gregorio Maranon
Madrid, Madrid, 28007
- Not yet recruiting
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28009
- Not yet recruiting
Clinica Universidad de Navarra (CUN)
Pamplona, Navarre, 31008
- Not yet recruiting
NEXT Oncology - Madrid
Pozuelo de Alarcón, Madrid, 28223
About this study
Official title: 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
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.
- Conditions
- Advanced Solid Tumor, Non-Small Cell Lung Cancer, Colorectal Neoplasms, Pancreatic Ductal Adenocarcinoma
- Being tested
- BLU-924
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Rectal Neoplasms, Pancreatic Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BLU-924Drug
Also called SAR449336
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy Part: BLU-924 Dose Escalation, Dose Enrichment, and Dose Expansion | Experimental | 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. Receives: Drug: BLU-924 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 5 years
Dose Escalation and Enrichment: Maximum Tolerated Dose (MTD) of BLU-924
Measured: Up to 5 years
Dose Escalation and Enrichment: Recommended Dose for Expansion (RDFE) of BLU-924
Measured: Up to 5 years
Dose Expansion: Overall Response Rate (ORR)
Measured: Up to 5 years
Secondary outcomes (13)
Dose Escalation and Enrichment: Overall Response Rate (ORR)
Measured: Up to 5 years
Dose Escalation, Enrichment, and Expansion: Duration of Response (DOR)
Measured: Up to 5 years
Dose Escalation, Enrichment, and Expansion: Disease Control Rate (DCR)
Measured: Up to 5 years
Dose Escalation, Enrichment and Expansion: Progression-free Survival (PFS)
Measured: Up to 5 years
Dose Expansion: Overall Survival (OS)
Measured: Up to 5 years
Dose Escalation, Enrichment and Expansion: AUC - Area Under the Plasma Concentration Time Curve for BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: Cmax - Maximum Plasma Concentration for BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: Cmin - Minimum Plasma Concentration of BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: Tmax - Time to Maximum Plasma Drug Concentration for BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: t1/2 - Terminal Half-life of BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: CL/F - Apparent Oral Clearance of BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: Vc/F- Apparent Volume of Central Compartment of BLU-924
Measured: Up to 2 years
Dose Escalation, Enrichment and Expansion: Vd- Volume of Distribution of BLU-924
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start4 Jun 2026
- Primary completionSep 2029 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 265 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Blueprint Medicines Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sanofi
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07629960
- Sponsor's protocol ID
- BLU-924-1101
- Status last verified
- Sep 2026
- First submitted
- 1 Jun 2026
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.