Ascentage Pharma: Olverembatinib (HQP1351) Data in GIST Published in Nature STTT

Publication of Phase Ib data shows promising activity and a novel mechanism for olverembatinib in SDH-deficient GIST; a registrational Phase III is underway.

Olverembatinib demonstrated an objective response rate of 23.1%, a clinical benefit rate of 84.6% (95% CI, 65.1-95.6), and a median progression-free survival of 25.7 months (95% CI, 12.9-not reached) in 26 patients with SDH-deficient GIST, with median follow-up of 14.5 months. The trial enrolled 66 patients overall and is described as the largest prospective study to date in this rare subtype. The report also states the drug was well tolerated. These are concrete clinical metrics that support activity in a population without established standard-of-care options.

The translational findings link SDH deficiency to dysregulated lipid metabolism and CD36 overexpression, and show olverembatinib inhibited CD36 and lipid uptake in tumor cells. The paper attributes antitumor effects to combined modulation of lipid metabolism plus inhibition of HIF, FGFR, and VEGFR pathways. This mechanistic data offers a plausible pharmacologic explanation for the clinical signals and creates a measurable biomarker axis (CD36/lipid uptake) to follow in future work. This is particularly important because SDH-deficient GIST presents a unique metabolic profile, potentially exploitable for targeted therapies.

From an investor perspective, Ascentage Pharma’s olverembatinib represents a significant opportunity in a niche oncology market with high unmet need. The Breakthrough Therapy Designation from the China CDE signals regulatory confidence in the drug’s potential. Key near-term items to watch include the international Phase III registrational study POLARIS-3 (NCT06640361) that is currently recruiting, and regulatory progress tied to the drug’s Breakthrough Therapy Designation from China’s CDE for SDH-deficient GIST after prior therapy. Monitor readouts and safety data from the Phase III and whether translational biomarkers (CD36 expression or lipid-uptake assays) appear in those protocols; these will materially affect regulatory and clinical interpretation within a typical pivotal-trial timeframe. Should POLARIS-3 confirm the Phase Ib findings, olverembatinib could become the new standard of care for this difficult-to-treat patient population, driving substantial revenue for Ascentage Pharma.