On June 4, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated clinical data of olverembatinib (HQP1351), a third-generation tyrosine kinase inhibitor (TKI), in patients with TKI-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST), in an oral report at the 60th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL (Press release, Ascentage Pharma, JUN 4, 2024, View Source;oral-report-released-latest-data-of-olverembatinib-in-sdh-deficient-gist-including-a-cbr-of-92-3-302164178.html [SID1234644099]). This is the third consecutive year in which clinical data from this study of olverembatinib were selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting.
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The ASCO (Free ASCO Whitepaper) Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world’s most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO (Free ASCO Whitepaper) Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company’s proprietary drug candidates selected for presentations, including an oral report, at ASCO (Free ASCO Whitepaper) 2024.
The oral report features the latest data that further validated the promising efficacy and manageable safety of olverembatinib in SDH-deficient GIST. The Phase I study enrolled a total of 26 patients with SDH-deficient GIST. Among these patients, 6 achieved partial responses (PR), 18 achieved stable diseases (SD) that lasted longer than four treatment cycles, with a clinical benefit rate (CBR) of 92.3% (24/26) and a median progression-free survival (PFS) of 25.7 months.
Olverembatinib, an orally-available novel TKI developed by Ascentage Pharma, is the first third-generation BCR-ABL inhibitor approved in China. At present, the drug is approved in China in two indications, including adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first-and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.
While being clinically developed and adopted for the treatment of hematologic malignancies, olverembatinib is also being clinically evaluated in patients with GIST. To date, olverembatinib has been granted a Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of patients with SDH-deficient GIST who had received first-line treatment.
"SDH-deficient GIST represents a treatment gap that urgently needs new treatment options," said Prof. Haibo Qiu, of Sun Yat-Sen University Cancer Center, and the presenter of the report. "In the study, olverembatinib has shown impressive clinical benefits in SDH-deficient GIST, including a median PFS of 25.7 months, as well as favorable safety and tolerability profiles. Moving forward, we will continue to evaluate the drug’s efficacy and safety in SDH-deficient GIST."
"Building on data released at the ASCO (Free ASCO Whitepaper) Annual Meeting in the past two years, results presented in the oral report this year continued to demonstrate promising clinical benefits and manageable safety of olverembatinib in SDH-deficient GIST," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by these results, as they signal a potential breakthrough in addressing another indication with an urgent unmet clinical need. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will press forward with this clinical development program in order to bring a safe and effective new treatment option to patients as soon as possible."
Highlights of these data presented at ASCO (Free ASCO Whitepaper) 2024 are as follows:
Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST)
Abstract#: 11502
Session Title: Sarcoma
Date and Time: June 3, 2024, Monday, 3:00 PM – 6:00 PM (Central Time)
First Author: Haibo Qiu, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
Highlights:
Background: SDH-deficient GIST is a subset of wild-type GIST that constitutes approximately 10% of GISTs. In the National Comprehensive Cancer Network (NCCN) guidelines, there is no preferred regimen for SDH-deficient GIST, thus indicating an urgent unmet medical need. Olverembatinib, approved in China for the treatment of patients with chronic myeloid leukemia, has shown promising clinical efficacy in SDH-deficient GIST. In this abstract, the study reports updated efficacy data of olverembatinib in SDH-deficient GIST.
Introduction: The aim of this study was to evaluate the safety and efficacy (per RECIST v1.1) of olverembatinib in patients with SDH-deficient GIST and other solid tumors. Olverembatinib was administered orally once every other day (QOD) in 28-day cycles.
Patient enrollment and methods: As of December 27, 2023, 26 patients with SDH-deficient GIST (confirmed by immunohistochemistry [IHC] assay) had received ≥1 dose of olverembatinib (median [range] age, 30 [13-56] years), and 25 of them had received 1-4 tyrosine kinase inhibitors (TKIs; 50.0%% [13/26] of patients received ≥3 TKIs). Olverembatinib was administered OQD in doses ranging from 30 to 50 mg (30 mg [n = 6]; 40 mg [n = 14]; 50 mg [n = 6]).
Efficacy Results: In the 26 patients with SDH-deficient GIST, the median (range) duration of treatment was 15.6 (1.8-42.3) months. 6 of these patients achieved partial responses (PR); and another 18 patients achieved stable diseases (SD) lasting > 4 cycles. The clinical benefit rate (CBR, complete response [CR] + PR + SD > 4 cycles) was 92.3% (24/26), the longest treatment duration was 40 months, and the median (range) PFS was 25.7 months (12.9-not reached [NR]).
Safety results: The adverse event profile was the same as previously reported (Qiu H, et al, J Clin Oncol 41:11540), with no newly emergent safety issues observed.
Conclusions: Olverembatinib was well tolerated. In patients with SDH-deficient GIST, olverembatinib demonstrated a CBR exceeding 90% and significantly prolonged the estimated median PFS, indicating the potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GIST.
*Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland.
Appendix: The four clinical studies of Ascentage Pharma’s three drug candidates, including lisaftoclax, presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.
Drug Candidates
Abstract Title
Abstract#
Format
Olverembatinib (HQP1351)
Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) and paraganglioma.
#11502
Oral
Report
Lisaftoclax
（APG-2575）
Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia.
#6541
Poster Presentation
Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).
#7078
Poster Presentation
APG-2449
Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.
#3124
Poster Presentation