An International, Multicenter, Open-label, Randomized, Phase 3 Study of BLU-285 vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic Gastrointestinal Stromal Tumor (GIST)
Overview
- Phase
- Phase 3
- Intervention
- avapritinib
- Conditions
- GIST
- Sponsor
- Blueprint Medicines Corporation
- Enrollment
- 476
- Locations
- 112
- Primary Endpoint
- Efficacy of Avapritinib Based on Progression-free Survival (PFS) Determined by Central Radiological Assessment Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), Version 1.1
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is an open-label, randomized, Phase 3 study in patients with locally advanced unresectable or metastatic GIST (advanced GIST) of avapritinib (also known as BLU-285) versus regorafenib in patients previously treated with imatinib and 1 or 2 other TKIs.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients who are ≥ 18 years of age.
- •Patients who have histologically confirmed metastatic or unresectable GIST.
- •Patients who received imatinib and 1 or 2 other TKIs as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective disease progression prior to enrollment onto BLU-285-1303 study.
- •Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.
Exclusion Criteria
- •Patients who have received prior treatment with avapritinib or regorafenib.
- •Patients who have previously received more than 3 different TKI treatment regimens.
- •Patients who are known to be both V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor alpha (PDGRFα) wild type.
- •Patients who received any systemic anticancer therapy within 1 week before the first dose of study drug.
- •Patients who have clinically significant cardiovascular disease
- •Patients have experienced arterial thrombotic or embolic events within 6 months before the first dose of study drug, or venous thrombotic events within 14 days of the first dose of study drug
- •Patients who have experienced any hemorrhage or bleeding event NCI CTCAE version 5.0 Grade 3 or higher within 4 weeks before the first dose of study drug
- •Patients who have a known risk of intracranial bleeding, or a history of intracranial bleeding within 1 year prior to the first dose of study drug
- •Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal perforation, or bone fracture.
- •Patients who have poor organ function as defined by laboratory parameters specified in the protocol.
Arms & Interventions
avapritinib
300 mg PO QD
Intervention: avapritinib
regorafenib
160 mg PO QD
Intervention: regorafenib
Outcomes
Primary Outcomes
Efficacy of Avapritinib Based on Progression-free Survival (PFS) Determined by Central Radiological Assessment Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), Version 1.1
Time Frame: 24 Months
To demonstrate the efficacy of avapritinib based on progression-free survival (PFS) determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following 2 or 3 regimens of prior treatment with a tyrosine kinase inhibitor (TKI), including imatinib, compared to patients treated with regorafenib. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
Secondary Outcomes
- Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1(24 Months)
- Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib(24 Months)
- European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30). Change in Individual Scores in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib(Difference between baseline and week 12 of treatment)