(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors
Condition: Gastrointestinal Stromal Tumors (GIST); Other Relapsed or Refractory Solid Tumors
MeSH terms: Neoplasms; Gastrointestinal Stromal Tumors
Intervention: Avapritinib
Intervention description: avapritinib tablets
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Dose Escalation and Dose Expansion
Masking: None (Open Label)
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 2L GIST; GIST second line; GIST gleevec; GIST imatinib; Second-line GIST clinical trial; 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 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).
    

Eligibility 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.