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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
265
Tablet
Florida Cancer Specialists & Research Institute - Sarasota
Sarasota, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGMary Bird Perkins Cancer Center
Baton Rouge, Louisiana, United States
NOT_YET_RECRUITINGMassachusetts General Hospital - Main Campus
Boston, Massachusetts, United States
NOT_YET_RECRUITINGUniversity of Michigan Medical School Rogel Cancer Center
Ann Arbor, Michigan, United States
NOT_YET_RECRUITINGHackensack University Medical Center
Hackensack, New Jersey, United States
NOT_YET_RECRUITINGNYU Langone Health Perlmutter Cancer Center
New York, New York, United States
NOT_YET_RECRUITINGTennessee Oncology, PLLC
Nashville, Tennessee, United States
NOT_YET_RECRUITINGThe University of Texas MD Anderson Cancer Center - Texas Medical Center
Houston, Texas, United States
NOT_YET_RECRUITINGNext Oncology Virginia Cancer Specialist
Fairfax, Virginia, United States
RECRUITING...and 6 more locations
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.