China CDE Approves Phase III Study of Olverembatinib for SDH-Deficient GIST

June 10, 2024 — Ascentage Pharma (6855.HK), a biopharmaceutical company specializing in innovative treatments for cancer, chronic hepatitis B (CHB), and age-related conditions, revealed that China's Center for Drug Evaluation (CDE) has authorized a global Phase III study for its novel drug olverembatinib (HQP1351). This drug targets patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who have not responded to prior treatments. This approval is a significant milestone in Ascentage Pharma's journey in solid tumor therapy development.

The approved Phase III study is global, multicenter, single-arm, and open-label, and it aims to assess the efficacy and safety of olverembatinib in SDH-deficient GIST patients. The CDE has agreed that the study results can be used to support a future New Drug Application (NDA) for the treatment in SDH-GIST.

GIST is the most prevalent type of soft tissue sarcoma originating in the gastrointestinal tract, with a global incidence of about 1-1.5 per 100,000 annually. The key genetic drivers of GIST are mutations in KIT and PDGFRA, present in 85%-90% of these patients. Tyrosine kinase inhibitors (TKIs) have improved the prognosis for these patients. However, around 85% of pediatric and 10%-15% of adult GIST patients lack these mutations, classifying them as wild-type GIST. Within this group, SDH-deficient and non-SDH-deficient GISTs are further classified based on SDH expression loss.

SDH-deficient GIST has distinct clinical and pathological features. Typically diagnosed at a median age of 21 and more frequent in women, SDH-deficient GIST often originates in the stomach and has a high likelihood of metastasizing. The condition is marked by the loss of SDHB protein expression in immunohistochemistry assays. Early-stage localized SDH-deficient GIST can be surgically treated, but relapses are common, and there are no standard treatment options for advanced or relapsed cases. Imatinib and other TKIs have shown limited efficacy, with a five-year event-free survival rate of just 24%. Patients, often young, face significant life quality and survival impacts, highlighting the urgent need for new treatment options.

Olverembatinib, an orally-administered third-generation TKI, has shown promising results. It has been granted Breakthrough Therapy Designation by China's CDE for treating SDH-deficient GIST following first-line treatment. As a multi-targeted TKI, olverembatinib has demonstrated notable efficacy and safety in these patients. Recognized at the American Society of Clinical Oncology (ASCO) Annual Meetings for three consecutive years since 2022, the latest results presented showed a clinical benefit rate (CBR) of 92.3%.

Olverembatinib is the first China-approved third-generation BCR-ABL inhibitor. It has been sanctioned in China for adult patients with TKI-resistant chronic-phase or accelerated-phase chronic myeloid leukemia (CML) harboring the T315I mutation and those resistant to or intolerant of first- and second-generation TKIs. It is jointly commercialized by Ascentage Pharma and Innovent Biologics.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, expressed optimism about the Phase III study approval, seeing it as a potential clinical breakthrough for a condition lacking treatments and a significant step in Ascentage Pharma's solid tumor therapy development. The company remains dedicated to addressing unmet clinical needs globally and aims to expedite this clinical program to benefit more patients.

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