(navigator) study of blu-285 in patients with gastrointestinal stromal tumors (gist) and other relapsed and refractory solid tumors

Conditions: Gastrointestinal Stromal Tumors (GIST); Other Relapsed or 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 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.

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