Olverembatinib leads to a clinical benefit rate of 83.3% in patients with gastrointestinal stromal tumors (GISTs) who were resistant to or failed prior treatment with tyrosine kinase inhibitors, according to results from a phase 1b/2 clinical trial presented at the 58th American Society of Clinical Oncology (ASCO) Annual Meeting.

The open-label, multicenter trial evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of olverembatinib in patients with locally advanced or metastatic GISTs whose disease was resistant or failed to respond to imatinib or other tyrosine kinase inhibitors.

A total of 39 patients were given oral olverembatinib once every 2 days in repeated cycles of 28 days. Of these, 31 had a mutation in the KIT or PDGFRA genes while 8 had wild-type GISTs. Of these 8 patients, 6 were succinate dehydrogenase-deficient. 

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Of the patients with KIT or PDGFRA mutations, the best response was stable disease seen in 13 patients. Eight of the remaining patients withdrew early from the study while 10 had the progressive disease before the third cycle.

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Of patients with wild-type GISTs, 2 had partial responses, the tumor of 1 patient shrunk by 35.9% while another shrunk by 54.2%. Four patients had stable disease as the best response for 2, 6, 14, and 36 cycles, respectively.

The majority of patients (92.3%) had treatment-emergent adverse events. Most of these were mild or moderate. Common treatment-related adverse events included increased leukocyte and neutrophil counts, anemia, constipation or asthenia, hyperuricemia, hypoalbuminemia, and elevated aspartate aminotransferase or alanine transaminase levels.

“These clinical data presented at this year’s ASCO meeting show that olverembatinib also has clinical potential for the treatment of GIST, thus suggesting a wide therapeutic window for the drug candidate as a multi-kinase inhibitor,” said Yifan Zhai, MD, PhD, chief medical officer of Ascentage Pharma, in a press release.

Olverembatinib is a novel tyrosine kinase inhibitor being developed by Ascentage Pharma for the treatment of GIST and other types of cancer. It has already been approved in China to treat adults with tyrosine kinase inhibitor-resistant chronic-phase chronic myeloid leukemia or accelerated-phase CML with the T315I mutation.


ASCO 2022 | The first dataset of olverembatinib (HQP1351) in patients with GIST demonstrates therapeutic potential with a clinical benefit rate of 83.3%. News release. Ascentage Pharma; June 6, 2022.