(VOYAGER) Study of Avapritinib vs Regorafenib in Patients With Locally Advanced Unresectable or Metastatic GIST
Condition: GIST
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: avapritinib; regorafenib
Intervention description: Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously.; 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).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 476.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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; PDGFRA

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients who are ≥ 18 years of age.

          2. Patients who have histologically confirmed metastatic or unresectable GIST.

          3. 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.

          4. Patients who have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
             of 0 to 1.

        Exclusion Criteria:

          1. Patients who have received prior treatment with avapritinib or regorafenib.

          2. Patients who have previously received more than 3 different TKI treatment regimens.

          3. 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.

          4. Patients who received any systemic anticancer therapy within 1 week before the first
             dose of study drug.

          5. Patients who have clinically significant cardiovascular disease

          6. 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

          7. 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

          8. 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

          9. Patients who have a symptomatic non-healing wound, ulcer, gastrointestinal
             perforation, or bone fracture.

         10. Patients who have poor organ function as defined by laboratory parameters specified in
             the protocol.

         11. Patients who have received neutrophil growth factor support within 14 days of first
             dose of study drug.

         12. Patients who require therapy with a concomitant medication that is a strong inhibitor
             or strong inducer of CYP3A4.

         13. 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.

         14. 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.

         15. Patients who have a history of a seizure disorder requiring anti-seizure medication.

         16. Patients who have metastases to the brain.

         17. Patients who have a QT interval corrected using Fridericia's formula (QTcF) of > 450
             msec.

         18. 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.

         19. Women who are pregnant.

         20. Women who are breastfeeding.

         21. Patients who have prior or ongoing clinically significant illness, medical condition,
             surgical history, physical finding, or laboratory abnormality as determined by the
             investigator.