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Patients receive avapritinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Avapritinib

Jordi Rodon Ahnert

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.

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.

Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors

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

ORR defined as confirmed complete response (CR) or partial response (PR) from the time of study treatment initiation until disease progression as centrally assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology Criteria (RANO) criteria, as appropriate. Confirmed CR or PR will be defined as a repeat assessment performed 4 weeks (+/-3 days) after the criteria for response is first met. Will estimate ORR along with 90% confidence interval according to Clopper-Pearson method for each cohort and for specific tumor type.

Determined for patients with best overall response of confirmed CR or PR (centrally assessed); DoR is defined as the number of months from the start of CR or PR (whichever response is recorded first) and subsequently confirmed to the first date of documented PD or death. Descriptive statistics will be used.

DCR defined as BOR of confirmed CR or PR (either of any duration) or stable disease SD \>= 16 weeks following study treatment initiation. Descriptive statistics will be used.

Will be measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics will be used.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for locally advanced primary malignant central nervous system neoplasm