This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (formerly BLU-285), administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).
Name: Avapritinib
Description: Either complete response (CR) or partial response (PR)
Measure: Part 2: Overall response rate Time: At Cycle 3 Day 1, then every 2 cycles through Cycle 13, then every 3 cycles thereafter.Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)
Measure: Maximum plasma concentration of avapritinib Time: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)
Measure: Time to maximum plasma concentration of avapritinib Time: Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)Description: CR, PR and stable disease (SD)
Measure: Duration of response Time: Overall median and at 3, 6, and 12 monthsDescription: Rate of CR, PR, and SD
Measure: Clinical benefit rate Time: 16 weeksAllocation: N/A
Single Group Assignment
There is one SNP
OR For Part 2: - Group 1: Patients must have a confirmed diagnosis of unresectable GIST that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib, or an experimental kinase-inhibitor agent, and the patient does not have a D842V mutation in PDGFRα. --- D842V ---
- Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. --- D842V ---
Patients must not have a known D842V mutation in PDGFRα. --- D842V ---