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
Next Oncology Virginia Cancer Specialist
Fairfax, Virginia, United States
RECRUITINGDose 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
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