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Clinical Trial 19504

Cancer Type: Sarcoma
Interventions:Avapritinib; BAY 73-4506 (Regorafenib); BLU-285 (Avapritinib); Not Applicable; Regorafenib (Stivarga)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Mihaela Druta

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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)

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.

Objective

Primary Objective: -The primary objective is to demonstrate the efficacy of avapritinib based on progression-free survival (PFS) determined by central radiological assessment per mRECIST, version 1.1 in patients with advanced GIST following 2 or 3 regimens of prior treatment, including imatinib, compared to patients treated with regorafenib. Secondary Objectives: The key secondary objectives are: -To evaluate objective response rate (ORR) determined by central radiology assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 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. -To evaluate the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) physical functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To evaluate the EORTC-QLQ-C30 pain score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To evaluate the EORTC-QLQ-C30 role functioning score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To evaluate the EORTC-QLQ-C30 appetite loss score in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. To preserve study-wide Type I error, the key secondary objectives will be tested in the order presented, as part of the sequential testing scheme for the study if the primary analysis is significant. Additional secondary objectives are: -To evaluate the safety and tolerability of avapritinib compared to regorafenib. -To evaluate disease response rate as assessed by the Investigator per mRECIST, version 1.1 and determined by central radiological assessment per Choi criteria in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To evaluate disease control rate (DCR) per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To evaluate duration of response (DOR) per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib. -To demonstrate the effect of avapritinib as measured by the EORTC-QLQ-C30 scores not included in the key secondary objectives in patients with advanced GIST compared to patients treated with regorafenib. -To determine steady state systemic exposure of avapritinib. -To assess the patient reported perception of abdominal pain. Exploratory Objectives: The exploratory objectives are: -To correlate clinical efficacy with genetic subtype (KIT or PDGFRá) and other cancer-relevant gene mutant allele fractions measured in circulating tumor deoxyribonucleic acid (ctDNA) at Baseline. -To correlate clinical efficacy with changes in the mutant allele fractions measured in ctDNA during treatment with avapritinib. -To assess patient-reported perception of cognitive function in patients with advanced GIST treated with avapritinib compared to patients treated with regorafenib using Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scores. -To assess patient reported outcomes (PROs) using the Patient Global Impression of Severity (PGI-S) questionnaire, the Patient Global Impression of Change (PGI-C) questionnaire. -To assess health status using the EuroQoL 5 Dimension (EQ-5D-5L) assessment to support future health economic analyses.

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 for treatment of GIST, including TKIs used for adjuvant therapy. 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 2.

  • Exclusion Criteria

  • Patients who have received prior treatment with avapritinib or regorafenib.
  • Patients who have received more than 3 different prior 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 2 weeks before randomization.
  • Patients with clinically significant cardiovascular disease, thromboembolic disease, or significant risk of bleeding.
  • Patients who have a non-healing wound, ulcer, 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 randomization.
  • 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 randomization. Patient has significant traumatic injury within 28 days before randomization.
  • Patients who have a history of another primary malignancy that has been diagnosed or required therapy within 3 years before randomization.
  • 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 randomization and for at least 30 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 randomization and for at least 90 days after the last dose of study drug.
  • Women who are pregnant or breastfeeding.
  • Patients who have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality as determined by the investigator.