Phase 2 Study of Avapritinib in Patients With CKIT or PDGFRA Mutation-Positive Malignant Solid Tumors

• The patient (or legally acceptable representative if applicable) provides written informed consent for the study

• \>= 18 years of age on the day of informed consent signing

• Patient has a locally advanced or metastatic solid tumor and has progressed on appropriate standard therapy, has not shown clinically meaningful benefit to appropriate standard therapy, has no available standard therapy, or has declined appropriate standard therapy

⁃ NOTE: Specific solid tumor types include but are not limited to melanoma, breast cancer, lung cancer, gastroesophageal cancer, colorectal cancer, sarcoma, solid tumors not otherwise specified (NOS), and primary central nervous system (CNS) tumors. Patients with any other solid tumor type with the exception of gastrointestinal stromal tumor (GIST) will be eligible for enrollment in the study

• Measurable disease per the RECIST v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria, as appropriate (for Cohorts 1 and 2 only). NOTE: Patients in Cohort 3 can have measurable or non-measurable disease

• Documented pathogenic CKIT activating mutation (Cohort 1) OR pathogenic PDGFRA activating mutation (Cohort 2) based on tissue-based next-generation sequencing (NGS) diagnostic test (Oncomine Comprehensive Assay \[OCA\] or FoundationOne CDx) OR plasma cfDNA-detected (Guardant360) pathogenic CKIT or PDGFRA activating mutation (for patients with measurable disease) or tissue or cfDNA-detected pathogenic CKIT or PDGFRA activating mutation (for patients with non-measurable disease; Cohort 3). Mutation pathogenicity will be verified by the MD Anderson Cancer Center (MDACC) Precision Oncology Decision Support (PODS) team. Acceptable CKIT/PDGFRA mutations for study eligibility are listed in Appendix E.

• Has available archival tissue for CKIT or PDGFRA mutation testing (cohort 1 and 2 only).

• White blood cell count \> 2,500/uL and \< 15,000/uL (within 28 days of study treatment initiation)

• Absolute neutrophil count \>= 1.5 x 10\^9/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility) (within 28 days of study treatment initiation)

• Platelet count \>= 75 x 10\^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility) (within 28 days of study treatment initiation)

• Hemoglobin \>= 9.0 g/dL (without blood transfusion within 7 days of laboratory test used to determine eligibility) (within 28 days of study treatment initiation)

• Total bilirubin =\< 1.5 x upper limit of normal (ULN); if hepatic metastases are present, =\< 2.0 x ULN (within 28 days of study treatment initiation)

• Aspartate transaminase (AST) and alanine transaminase (ALT) =\< 2.5 x ULN; if hepatic metastases are present, =\< 5.0 x ULN (within 28 days of study treatment initiation)

• Serum creatinine \</= 2XULN or creatinine clearance ≥45 mL/min (within 28 days of study treatment initiation)

• Cardiac ejection fraction \>/= 45% per screening echocardiogram or multigated acquisition scan

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Life expectancy \>= 3 months

• Willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations

• Willing to undergo biopsy as required by the study

• Females must be postmenopausal (defined as \>= 45 years of age with at least 12 months of spontaneous amenorrhea) or premenopausal with documented surgical sterilization (tubal ligation, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or evidence of non-childbearing status for women of childbearing potential (negative serum beta-human chorionic gonadotropin pregnancy test) within 3 days of study treatment initiation

• Females of childbearing potential must either abstain from heterosexual intercourse or use a highly effective method of contraception for the course of the study through 6 weeks after the last dose of avapritinib.

• Males with female partners of reproductive potential must either abstain from sexual intercourse or they and their partners must use a highly effective method of contraception when engaging in sexual intercourse for the course of the study through 30 days after the last dose of study treatment