Live from ASCO 2024 | Oral Report Released Latest Data of Olverembatinib in SDH-Deficient GIST, Including a CBR of 92.3%

SUZHOU, China and ROCKVILLE, Md., June 4, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today 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) Annual Meeting taking place in Chicago, IL. This is the third consecutive year in which clinical data from this study of olverembatinib were selected for presentations at the ASCO Annual Meeting.

The ASCO 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 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 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 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 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 Annual Meeting.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials, including 5 global registrational phase III studies, in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases.

Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates.

Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

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