Suzhou, China, December 27^th, 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, announced today that the Clinical Cancer Research, an internationally renowned journal, has published the 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). This study has once again been recognized on a top-tier international academic platform, following its selection for presentation 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.

Dr. Jason Yang, CEO of CStone, said, “We are pleased to see the data of AYVAKIT published in a reputable oncology journal. This once again highlights the substantial potential of AYVAKIT for patients with advanced KIT-mutant GIST. AYVAKIT is the world’s first precision therapy approved for advanced GIST harboring the PDGFRA Exon 18 mutation. It's recent inclusion in the 2023 National Reimbursement Drug List enhances availability and affordability for patients. We remain committed to advancing the development of AYVAKIT in Greater China and exploring its therapeutic potential in other disease areas to benefit a broader patient population.”

Professor Li Jian from Peking University Cancer Hospital, the corresponding author of the article and a researcher of AYVAKIT study in China, said, “The publication of our research in Clinical Cancer Research shows the therapeutic potential of AYVAKIT in treating advanced GISTin patients with specific KIT mutations. Thesefindings strongly support the potential application of AYVAKIT among advanced GIST patients with various KIT mutations, supporting the expanding clinical value of AYVAKIT. We look forward to seeing AYVAKIT to benefit more patients in China.”

Professor Zhang Xinhua from the First Affiliated Hospital of Sun Yat-sen University, the first author of the article and a researcher of AYVAKIT study in China, said, “We are very pleased to see the new findings of AYVAKIT published in Clinical Cancer Research. The results of this analysis show promising prospects for AYVAKIT as a second-line treatment for patients with KIT AL^pos ABP^neg mutations and patients with KIT exon 9 mutation GIST in later lines (≥4L).”

The article presents post hoc analysis data from the global Phase 1 NAVIGATOR study and the Chinese bridging Phase 1/2 study CS3007-101, focusing on patients with advanced GIST. 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 AYVAKIT in Chinese patients with unresectable or metastatic GIST.

The results showed significantly more robust antitumor activity of AYVAKIT in patients with GIST harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; AL^pos ABP^neg) versus patients whose tumors harbored other KIT mutations. 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 AL^pos ABP^neg GIST and later lines of therapy for patients with KIT AL^pos ABP^neg or exon 9 mutational profiles.

A total of 160 patients with advanced KIT-mutant GIST were evaluated in the post hoc analysis, 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.

At baseline, 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 AL^pos ABP^neg group), while the remaining 100 patients were designated as KIT OTHERS.

Across all lines of therapy, the adjusted (inverse probability weighting of baseline characteristics; IPW_BL) median progression-free survival (mPFS) was longer for the AL^pos ABP^neg 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 IPW_BL- 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 AL^pos ABP^neg 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 the 2023 National Reimbursement Drug List (NRDL) has significantly 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 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 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.

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 14 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, CStone has received 13 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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