Menu
Recruiting NCT07629960

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

Phase I / Phase II Interventional Advanced Solid Tumor Non-Small Cell Lung Cancer Colorectal Neoplasms Pancreatic Ductal Adenocarcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: BLU-924.
Who it may be relevant to
Registry conditions: Advanced Solid Tumor, Non-Small Cell Lung Cancer, Colorectal Neoplasms, Pancreatic Ductal Adenocarcinoma. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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.

Interventions

  • Drug BLU-924
    Tablet

Primary outcome measures

  • Dose Escalation and Enrichment: Percentage of Participants with Dose-limiting Toxicity (DLTs) [Time frame: Up to 5 years]
  • Dose Escalation, Enrichment and Expansion: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs) and Serious AEs [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 outcome measures (12)
  • 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]

Eligibility criteria

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 1 center
  • Next Oncology Virginia Cancer Specialist — Fairfax

Identifiers

NCT: NCT07629960 · BLU-924-1101

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗