Avapritinib is generally well tolerated and has marked antitumor activity in Chinese patients with gastrointestinal stromal tumor (GIST) who have a D842V mutation in the PDGFRA gene, according to the results of phase 1/2 clinical trial published in The Oncologist. The treatment also showed “notable efficacy as fourth- or later-line monotherapy.”

The open-label, multicenter, single-arm trial comprised a dose-escalation phase for safety followed by a dose-determination phase in phase 1 and a dose-expansion phase for safety and efficacy in phase 2. Phase 2 enrolled patients with a D842V mutation in the PDGFRA gene and patients without the mutation who had received at least 3 lines of therapy.

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The primary endpoints were the recommended dose to be used in phase 2, safety, and objective response rate as assessed by the Independent Radiology Review Committee (IRRC).

The results showed that there were no dose-limiting toxicities. The recommended phase 2 dose was determined as being 300 mg orally once a day.

During the rest of the trial, 59 patients received this dose of treatment. Common grade 2 or higher treatment-related adverse events were anemia, low white blood cell and neutrophil counts, and high levels of bilirubin in the blood.

In patients with a D842V mutation, the IRRC-assessed objective response rate was 75% and the investigator-assessed objective response rate was 79%. The clinical benefit rate was 86%. The median durations of response and progression-free survival were not reached.

The IRCC-assessed objective response rate in patients who received at least 3 lines of treatment was 22%, while the investigator-assessed objective response rate in these patients was 35%.

The median progression-free survival was 5.6 months.

Avapritinib is a type 1 kinase inhibitor. It is designed to inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation.

References

Li J, Zhang X, Deng Y, et al. Efficacy and safety of avapritinib in treating unresectable or metastatic gastrointestinal stromal tumors: a phase I/II, open-label, multicenter study. Oncologist. Published online December 7, 2022. doi:10.1093/oncolo/oyac242

A study of CS3007 in subjects with gastrointestinal stromal tumor. ClinicalTrials.gov. February 5, 2020. Updated April 27, 2022. Accessed December 14, 2022.