PRIMARY OBJECTIVE:~I. To determine the objective response rate (ORR) of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO criteria (as appropriate).~SECONDARY OBJECTIVES:~I. To evaluate the duration of response (DoR) to avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors.~II. To evaluate the disease control rate (DCR) of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors.~III. To determine the safety and tolerability of avapritinib in patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors, as assessed by the National Cancer institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.~EXPLORATORY OBJECTIVES:~I. To evaluate the overall survival (OS) of patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors receiving avapritinib.~II. To evaluate the ORR and DoR of avapritinib in patients with measurable brain or central nervous system (CNS) metastases at baseline.~III. To evaluate the progression-free survival (PFS) of patients with pathogenic CKIT or PDGFRA activating mutation-positive malignant solid tumors receiving avapritinib.~IV. To evaluate the correlation between genomic mutations and clinical outcome. V. To evaluate time on treatment (including patients treated beyond progression).~VI. To evaluate baseline genomics and circulating cell-free deoxyribonucleic acid (cfDNA) and functional analyses of variants.~OUTLINE:~Patients receive avapritinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days and then every 8 weeks.
This phase II trial studies the effect of avapritinib in treating malignant solid tumors that have a genetic change (mutation) in CKIT or PDGFRA and have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Avapritinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Avapritinib may help to control the growth of malignant solid tumors.