CStone Pharmaceuticals (SUZHOU) Co., Ltd. presented positive results at the 2020 Chinese Society of Clinical Oncology (CSCO) Annual Meeting from a phase I/II bridging study in China evaluating avapritinib in patients with unresectable or metastatic gastrointestinal tumors (GIST). Avapritinib was developed by CStone's partner, Blueprint Medicines.
This open-label, multicenter phase I/II bridging study was designed to evaluate the safety, pharmacokinetics, and anti-tumor activity of oral avapritinib in Chinese patients with unresectable or metastatic GIST. The recommended phase II dose (RP2D) was determined from preliminary results in the phase I dose-escalation study.
a) As of a data cutoff date of March 31, 2020, a total of 50 Chinese patients were enrolled and included in the safety evaluation of avapritinib. Eight patients with PDGFRA D842V mutant GIST and 23 patients with ≥3 prior lines of therapy were evaluable for response by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. As of the data cutoff date, 6 patients received avapritinib at 200 mg once daily (QD) doses, and 44 patients received avapritinib at 300 mg QD doses. Data from the Phase I study of avapritinib showed a well-tolerated safety profile at both the 200 mg and 300 mg QD doses, and no dose-limiting toxicity was observed in the study. The RP2D of avapritinib in the Phase II study of Chinese GIST patients was 300 mg QD, consistent with the RP2D in the global NAVIGATOR Phase 1 trial of avapritinib in advanced GIST.
b) Preliminary results demonstrated the robust clinical activity of avapritinib in Chinese patients with GIST harboring the PDGFRA D842V mutation. Among 8 evaluable patients with PDGFRA D842V mutant GIST who received 300 mg QD doses of avapritinib, all of the patients had evidence of tumor regression in target lesions, and 5 patients achieved a partial response. The overall response rate (ORR) was 62.5% . The other 3 patients had stable disease. Avapritinib also showed an ORR of 26.1% in GIST patients previously treated with ≥3 lines of prior therapy (fourth-line GIST);
c) Avapritinib was generally well tolerated. Most treatment-related adverse events (AEs) were Grade 1-2. The most common treatment-related AEs were anemia and increased blood bilirubin. There were no Grade 4 or 5 TRAEs, and the most common Grade 3 treatment-emergent AE was anemia.
"Due to the very limited benefits from available treatment options for patients with GIST harboring PDGFRA D842V mutations, there is an urgent unmet clinical need for new therapies. Avapritinib has demonstrated outstanding anti-tumor activity and a well-tolerated safety profile in Chinese patients with advanced PDGFRA D842V mutant GIST," said Lin Shen, vice president of Peking University Cancer Hospital and Institute, "As a physician, I am very happy to see that GIST treatment has entered the era of precision therapy. I hope avapritinib will soon be approved and will become a new treatment option for GIST patients harboring PDGFRA D842V mutations."
"We are pleased to present the preliminary data for avapritinib, a precision therapy for GIST, from a Phase I/II bridging study in Chinese patients, at the 2020 CSCO Annual Meeting. Avapritinib was well tolerated in Chinese GIST patients and demonstrated potent clinical activity in patients with PDGFRA D842V mutant GIST," said Dr. Jason Yang, Chief Medical Officer of CStone. "CStone submitted a New Drug Application (NDA) for this agent to the Taiwan, China Food and Drug Administration (TFDA) and the China National Medical Products Administration (NMPA) in March and April of this year, respectively. In July 2020, we received priority review designation from the China NMPA. We are committed to working closely with regulatory authorities to bring avapritinib to Chinese patients as soon as possible."
About Avapritinib
Avapritinib is a kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) under the brand name AYVAKIT™ for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. ...
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