(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

• Status: Completed
• Trial end date: 2021-06-03
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Blueprint Medicines Corporation

Criteria

Inclusion Criteria:

• For Part 1: Histologically- or cytologically-confirmed diagnosis of unresectable GIST or another advanced solid tumor. Patients with unresectable GIST must have disease that has progressed following imatinib and at least 1 of the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an experimental kinase-inhibitor agent, or disease with a D842 mutation in the PDGFRα gene. Patients with an advanced solid tumor other than GIST must have relapsed or refractory disease without an available effective therapy.

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.

• Group 2: Patients must have a confirmed diagnosis of unresectable GIST with a D842V mutation in the PDGFRα gene. The PDGFRα mutation will be identified by local or central assessment, either in an archival tissue sample or a new tumor biopsy obtained prior to treatment with avapritinib.

• Group 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFRα.

• Groups 1, 2 and 3: At least 1 measurable lesion defined by mRECIST 1.1 for patients with GIST.

• Groups 1 and 2: A tumor sample (archival tissue or a new tumor biopsy) has been submitted for mutational testing.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

• QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds

• Platelet count <90,000/mL

• Absolute neutrophil count <1000/mL

• Hemoglobin <9 g/dL

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present

• Total bilirubin >1.5 × ULN; >3 × ULN with direct bilirubin, >1.5 × ULN in the presence of Gilbert's Disease

• Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min Brain malignancy or metastases to the brain

• History of a seizure disorder or requirement for anti-seizure medication

• Group 3: Patients known to be KIT wild type.