Ascentage Pharma Presents New Data on Olverembatinib's Efficacy in SDH-Deficient GIST at ESMO 2024

On September 13, 2024, Ascentage Pharma, a global biopharmaceutical company with operations in Rockville, Maryland, and Suzhou, China, shared significant clinical data regarding olverembatinib (HQP1351) at the 2024 European Society of Medical Oncology (ESMO) Congress. This novel drug candidate displayed promising results in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).

The data, presented in a Mini Oral session at ESMO, revealed that olverembatinib offers sustained clinical benefits for patients with SDH-deficient GIST. As of March 12, 2024, a total of 26 patients enrolled in the study, six of whom achieved partial responses. The objective response rate stood at 23.1%, and the median progression-free survival was 22 months. Furthermore, the mechanism of action studies highlighted that olverembatinib acts by modulating multiple signaling pathways linked to angiogenesis, apoptosis, proliferation, and survival.

Olverembatinib is an orally administered tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma. It is notable for being the first third-generation BCR-ABL inhibitor approved in China. Currently, it is approved for two indications in China: for adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) with the T315I mutation, and for adult patients with CML-CP resistant to or intolerant of first and second-generation TKIs. The drug is co-commercialized in China by Ascentage Pharma and Innovent Biologics and has not yet been approved by the US Food and Drug Administration (FDA).

Beyond hematologic indications, olverembatinib is also being evaluated as a treatment for GIST. It has been granted a Breakthrough Therapy Designation by China's National Medical Products Administration (NMPA) for patients with SDH-deficient GIST who have undergone first-line treatment. Recently, the China CDE gave clearance for olverembatinib to enter a Phase III registrational study for this patient group.

Prof. Haibo Qiu from Sun Yat-Sen University Cancer Center, who presented the data, emphasized the rarity of SDH-deficient GIST and the lack of standard treatment options for unresectable cases. He noted that the Phase I study showed encouraging clinical benefit data and insights into the drug's mechanism of action. The promising results support the commencement of a Phase III study aiming to provide a new therapeutic option for patients with SDH-deficient GIST.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, stated that the clinical data reaffirm the benefit and tolerability of olverembatinib in patients with SDH-deficient GIST. He expressed hope that the continued development of this drug would soon provide a safe and effective treatment option for these patients.

As a premier oncology congress, the ESMO Congress provides a platform for showcasing groundbreaking cancer research. This year's highlights included the updated efficacy results of olverembatinib in SDH-deficient GIST patients, along with potential mechanisms of action.

In summary, the study results presented at ESMO 2024 indicate that olverembatinib offers sustained clinical efficacy in SDH-deficient GIST, modulating several signaling pathways critical to cancer development. This finding places olverembatinib as a potential new benchmark for the treatment of this rare cancer subtype and paves the way for future studies.