This is a Phase 1, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of avapritinib (also known as BLU-285), administered orally (PO), in adult patients with advanced systemic mastocytosis and other relapsed or refractory myeloid malignancies. The study consists of 2 parts, a dose-escalation part (Part 1) and an expansion part (Part 2).
Name: Avapritinib
Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1
Measure: Maximum plasma concentration of avapritinib Time: Every cycle (28 days) up to cycle 4Description: Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 8 and 24 hrs post dose (plus 10 and 48 hrs post dose in Part 2) on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1
Measure: Time to maximum plasma concentration of avapritinib Time: Every cycle (28 days) up to cycle 4Description: Including complete remission (CR), CR with partial recovery of peripheral blood (CRh), partial remission (PR) and clinical improvement (CI) using modified International Working Group Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European competence network on mastocytosis (ECNM) criteria; and duration of response (DOR)
Measure: Overall Response Rate Time: 8, 24, 40, 68 and every 24 weeks until patient terminates from the study (approximately 24 months)Description: Including morphologic complete remission (mCR), morphologic CR with partial recovery of peripheral blood (mCRh), and morphologic partial remission (mPR) based on Pure Pathologic Response
Measure: Morphologic response Time: ≥ 12 weeksDescription: Defined as change from Baseline
Measure: Changes in patient reported symptoms and quality of life using the Patient Global Impression of Symptom Severity (PGIS) scale Time: Part 2 only - Day 1 of Cycles 1-12Description: Defined as change from Baseline
Measure: Changes in patient reported quality of life using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C-30) Time: Part 2 only - Day 1 of Cycles 1-12Description: Defined as change from Baseline
Measure: Changes in patient reported outcomes using the advanced SM symptom assessment form (AdvSM-SAF) Time: Part 2 only - daily from Day -7 through Cycle 12Description: mL
Measure: Change in liver volume by imaging Time: Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)Description: mL
Measure: Change in spleen volume by imaging Time: Day 1 of Cycles 5-18, and every 6 cycles thereafter (each cycle is 28 days)Allocation: N/A
Single Group Assignment
There is one SNP
Changes in levels of serum tryptase and levels of V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) D816V allele burden in blood. --- D816V ---