Suzhou, China, June 6th, 2023—CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today announced that new data from a post hoc data analysis of the global Phase 1 NAVIGATOR and Phase 1/2 China bridging (CS3007-101) studies of AYVAKIT® (avapritinib) in advanced gastrointestinal stromal tumor (GIST) were presented in poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) annual meeting.
Discovered by CStone’s partner Blueprint Medicines, AYVAKIT is a potent, selective and orally available inhibitor of KIT and PDGFRA mutant kinases. CStone has an exclusive collaboration and license agreement with Blueprint Medicines for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan.
The results demonstrate significantly more robust antitumor activity of AYVAKIT in patients with KIT activation loop-positive, ATP binding pocket-negative (ALpos ABPneg) GIST versus patients whose tumors harbored other KIT mutational profiles. It was also observed that AYVAKIT could confer meaningful clinical benefits in patients with GIST harboring specific KIT mutation types, especially KIT activation loop (KIT-AL) or exon 9 mutations. Additionally, the data support AYVAKIT as a potential treatment option for second-line patients with KIT ALpos ABPneg GIST and later lines of therapy for patients with KIT ALpos ABPneg or exon 9 mutational profiles.
Dr. Jason Yang, CEO of CStone, said, “The new data presented at this ASCO meeting further highlight the significant potential of AYVAKIT to shift the treatment paradigm to precision therapy approaches for patients with advanced GIST. As a biopharmaceutical company focusing on immuno-oncology therapies and precision medicines, CStone is dedicated to offering first-in-class and best-in-class drugs for cancer patients. We will continue to advance the development of AYVAKIT in Greater China and explore its therapeutic potential to benefit broad range of patient populations.”
Dr. Josh Zhou, Greater China General Manager and Head of Commercial of CStone, said, “AYVAKIT is the first precision therapy approved to treat a genomically defined population of patients with advanced PDGFRA exon 18-mutant GIST. In Greater China, AYVAKIT is now available in over 80 hospitals and DTP pharmacies and has been included in more than 90 commercial insurance programs. We will strive to enhance the accessibility and affordability of AYVAKIT, enabling more patients to benefit from this first-in-class precision therapy.”
Professor Shen Lin, the Principal investigator of AYVAKIT study in China, and Deputy Director of Peking University Cancer Hospital, said, “We are pleased to present the latest clinical data on AYVAKIT in GIST at the 2023 ASCO meeting. The study results further demonstrate the therapeutic potential of AYVAKIT in treating patients with advanced GIST harboring specific types of KIT mutations. We are encouraged by the clinical benefits that AYVAKIT may bring to patients in China.”
The global NAVIGATOR study (NCT02508532) is a Phase 1, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antineoplastic activity of AYVAKIT, administered orally (PO), in adult patients with unresectable GIST or other relapsed or refractory solid tumors. The China bridging 1/2 study (NCT04254939; CS3007-101) is a Phase 1/2, open-label, multicenter clinical trial designed to evaluate the safety, PK and clinical efficacy of avapritinib in Chinese patients with unresectable or metastatic GIST.
A total of 160 patients with advanced KIT-mutant GIST were evaluated in the post hoc analysis reported at ASCO, with 131 patients from the NAVIGATOR study and 29 patients from the CS3007-101 study. The median follow-up duration for this patient population was 22.0 months (95% CI 18.3–27.4). The data cutoff date for the NAVIGATOR study was March 31, 2021, and for the CS3007-101 study was June 30, 2021.
KIT-AL mutations were more frequently detected (n=74, 46.3%) compared to KIT ATP-binding pocket (ABP) mutations (n=34, 21.3%). Among the patients, 60 patients (37.5%) had KIT-AL mutations without KIT-ABP mutations (the ALposABPneg group), while the remaining 100 patients were designated as KIT OTHERS.
Across all lines of therapy, the adjusted (inverse probability weighting of baseline characteristics; IPWBL) median progression-free survival (mPFS) was longer for the ALpos ABPneg group than for the KIT OTHERS group (9.1 vs 3.4 months; HR=0.47, 95% CI 0.32–0.68; P<0.0001), and the IPWBL- adjusted objective response rate (ORR) was higher (31.4% vs 12.1%; odds ratio 3.31, 95% CI 1.44–7.58; P=0.0047). The mPFS and ORR in the KIT ALposABPneg group were 19.3 months and 38.5%, respectively, in the second-line setting (n=13) and 11.0 months and 36.4%, respectively, in Chinese patients (lines 3–9, n=11). In patients with KIT exon 9 mutations in the fourth-line setting (n=14) and beyond (n=19), the mPFS was 5.6 and 3.7 months, respectively.
AYVAKIT is approved in Mainland China for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA exon 18 mutation, including PDGFRA D842V mutations. As part of the company’s commercialization efforts in Greater China, CStone has helped advance the clinical implementation of precision medicine approaches through physician engagement and continuous education, collaborations with industry associations, and partnerships with diagnostic companies. The inclusion of AYVAKIT in commercial insurance programs has expanded its accessibility and affordability to patients. It has been recommended in multiple domestic and international guidelines, including the Chinese Guidelines for the Diagnosis and Treatment of Systemic Mastocytosis in Adult Patients.
About AYVAKIT® (avapritinib)
AYVAKIT is a precision therapy approved by the National Medical Products Administration (NMPA) of China for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA exon 18 mutation, including PDGFRA D842V mutations. AYVAKIT was approved by the Department of Health (DOH), Hong Kong, China, and Taiwan Food and Drug Administration (TFDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA D842V mutation.
AYVAKIT is approved by the U.S. Food and Drug Administration (FDA) for the treatment of three indications: adults with indolent systemic mastocytosis (ISM), adults with advanced systemic mastocytosis (advanced SM), including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. This medicine is approved in Europe (AYVAKYT®) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S., Europe or Greater China.
About CStone
CStone (HKEX: 2616) is a biopharmaceutical company focused on research, development, and commercialization of 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 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, CStone has received ten NDA approvals for its four drugs. Multiple late-stage drug candidates are now under pivotal clinical trials or registration. CStone’s vision is to bring innovative oncology therapies to cancer patients worldwide.
For more information about CStone, please visit www.cstonepharma.com.
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