CStone Announces Preliminary Results from a Bridging Study of Avapritinib in Chinese Patients with Unresectable or Metastatic Gastrointestinal Stromal Tumors at the 2020 CSCO Annual Meeting

Avapritinib has demonstrated strong anti-tumor activity in Chinese patients with PDGFRA D842V mutant GIST

Avapritinib was generally well tolerated in Chinese GIST patients,consistent with the safety profile demonstrated in global studies

SUZHOU,China,Sept. 25,2020 -- CStone Pharmaceuticals (SUZHOU) Co.,Ltd. ("CStone",HKEX: 2616) 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 profileat 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 activityof 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 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. Previously,the U.S. FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of adult patients with unresectable or metastatic GIST harboring the PDGFRA D842V mutation.

Avapritinib is not approved for the treatment of any other indication in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing avapritinib globally for patients with advanced and indolent systemic mastocytosis (SM). The FDA granted breakthrough therapy designation to avapritinib for the treatment of advanced SM,including the subtypes of aggressive SM,SM with an associated hematologic neoplasm and mast cell leukemia.

CStone and Blueprint Medicines have an exclusive collaboration and license agreement for the development and commercialization of avapritinib and certain other drug candidates in Mainland China,Hong Kong,Macau,and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

CStone submitted an NDA for avapritinib to the TFDA and the China NMPA in March and April 2020,respectively,for the treatment of adult patients with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation. In July 2020,avapritinib received priority review designation from the China NMPA.

About GIST

GIST is a sarcoma,or tumor of bone or connective tissue,of the GI tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80,and diagnosis is typically triggered by GI bleeding,incidental findings during surgery or imaging and,in rare cases,tumor rupture or GI obstruction.

About 5 to 6 percent of primary GIST cases are caused by a PDGFRA D842V mutation,the most common PDGFRA exon 18 mutation. Prior to the FDA approval of AYVAKIT,there were no highly effective treatments for PDGFRA D842V mutant GIST in the U.S. Published data have shown poor outcomes in patients with PDGFRA D842V mutant GIST treated with imatinib and other approved therapies,including a median overall survival of 15 months,a median progression-free survival of 3 months and an overall response rate of 0 percent.[1]

About CStone

CStone Pharmaceuticals (HKEX: 2616) is a biopharmaceutical company focused on developing and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015,CStone has assembled a world-class management team with extensive experience in innovative drug development,clinical research,and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently,5 late-stage candidates are at pivotal trials. With an experienced team,a rich pipeline,a robust clinical development-driven business model and substantial funding,CStone's vision is to become globally recognized as a leading Chinese biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

Forward-looking Statement

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law,we undertake no obligation to update or revise publicly any forward-looking statements,whether as a result of new information,future events or otherwise,after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article,statements of,or references to,our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

[1]Cassier PA,Fumagalli E,Rutkowski P.,et al. Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin Cancer Res. 2012;18(16):4458-4464.