(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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GIST

Intervention / Treatment
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* Drug: avapritinib
* Drug: regorafenib


Participation Criteria
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Eligibility Criteria
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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. Patients who have received neutrophil growth factor support within 14 days of first dose of study drug. Patients who require therapy with a concomitant medication that is a strong inhibitor or strong inducer of CYP3A4. Patients who have had a major surgical procedure within 14 days of the first dose of study drug. Patient has significant traumatic injury within 28 days before the first dose of study drug. Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before first dose of study drug. Patients who have a history of a seizure disorder requiring anti-seizure medication. Patients who have metastases to the brain. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450 msec. Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 60 days after the last dose of study drug. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception from the time of the first dose of study drug and for at least 90 days after the last dose of study drug. Women who are pregnant. Women who are breastfeeding. Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: avapritinib<br>300 mg PO QD | Drug: avapritinib<br>* Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.<br>* Other names: BLU-285;|
| Active Comparator: regorafenib<br>160 mg PO QD | Drug: regorafenib<br>* Regorafenib tablets for oral administration. Regorafenib will be dosed at 160 mg once daily for 3 weeks out of every 4 weeks (ie. 3 weeks on/1 week off).<br>* Other names: Stivarga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Determined by Central Radiology Assessment Per mRECIST, Version 1.1 | To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. A complete response (CR) per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response (PR) is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR | 24 Months | 
| Overall Survival (OS) in Patients With Advanced GIST Treated With Avapritinib Compared to Patients Treated With Regorafenib | To evaluate 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 | The Global Health Status Score is derived from question 29 and 30 on the EORTC-QLQ-C30 tool. The change in score was assessed between baseline and week 12 in patients treated with advanced GIST treated with avapritinib compared to patients treated with regorafenib. The Global Health Status Score score range is 0 to 100 with a higher score indicating better global health status. A positive change indicates improvement in global health status. | Difference between baseline and week 12 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDGFRA, Other Relapsed or Refractory Solid Tumors, BLU-285, BLU 285, BLUE-285, BLUE 285, Avapritinib, GIST imatinib relapse, GIST gleevec relapse, GIST KIT, GIST relapse, GIST refractory, GIST imatinib intolerance, GIST TKI treatment, GIST tyrosine kinase inhibitor treatment, GIST TKI, GIST tyrosine kinase inhibitor, Advanced GIST, GIST mutations, GIST treatments, Blueprint GIST, Relapsed GIST clinical trial, Refractory GIST clinical trial, KIT-mutant GIST, cancer gist, gastrointestinal stromal tumor, gist cancer