Patient case: 62-year-old female with mucosal melanoma; genetic feature: KIT (L576P), KIT amplification

Clinical trial: (NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors

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: 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.

Relevance to patient case: not relevant