Live from ASCO 2023 | For the Third Consecutive Year, Ascentage Pharma Releases Promising Results of Alrizomadlin plus Pembrolizumab in Patients with Cutaneous Melanoma that Failed Immuno-Oncologic (IO) Therapies

SUZHOU, China, and ROCKVILLE, Md., June 5, 2023 /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 results from a Phase II study of MDM2-P53 inhibitor, alrizomadlin (APG-115), in combination with pembrolizumab in patients with unresectable or metastatic cutaneous melanoma that had failed immuno-oncologic (IO) drugs in a Poster Presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting. This data readout marks the third consecutive year in which updated results from this clinical study of alrizomadlin, a key drug candidate in Ascentage Pharma's apoptosis-targeted pipeline, were released at the ASCO Annual Meeting.

Showcasing progress in clinical development at the ASCO Annual Meeting for six consecutive years, Ascentage Pharma had clinical results from four clinical studies of four of the company's lead drug candidates selected for presentations in 2023. Among these results, the data of alrizomadlin in combination with pembrolizumab have demonstrated efficacy in patients with relapsed or IO drug-resistant cutaneous melanoma, with 2 complete responses (CRs) and 4 partial responses (PRs) that resulted in an overall response rate (ORR) of 23.1% in 26 efficacy evaluable patients.

The incidence of melanoma has risen persistently in recent years. According to global cancer data, more than 320,000 newly diagnosed cutaneous melanoma cases and approximately 60,000 cutaneous melanoma-related deaths were reported globally in 2020.^[1] Although IO drugs are playing a growing role in the treatment of advanced cutaneous melanoma, patients who failed therapy with IO drugs still lack effective clinical options.

"We continued to be encouraged by the efficacy and tolerability of alrizomadlin in combination with pembrolizumab in melanoma patients who progressed on prior PD-1 inhibitors," said Montaser F. Shaheen, MD, the Principal Investigator of this study from the University of Texas Health Science Center, San Antonio.

"As the first MDM2-p53 inhibitor entering clinical development in China and a China-developed novel therapeutic with first-in-class potential, alrizomadlin has once again demonstrated its clinical utility in patients with IO drug-resistant cutaneous melanoma," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Steadfastly committed to the mission of addressing unmet clinical needs in China and around the world, we will press ahead with this clinical development program which we hope will soon offer a new treatment option to patients in need."

* Alrizomadlin is an investigational drug that has not been approved in any country and region.

Highlights:

A phase 2 study of alrizomadlin (APG-115) in combination with pembrolizumab in patients with unresectable or metastatic cutaneous melanoma that has failed immuno-oncologic (IO) drugs.

• Abstract#: 9559
• Poster Board#: 322
• Session Title: Melanoma/Skin Cancers
• Key Results:
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- This open-label, multicenter Phase Ib/II study conducted in the U.S. and Australia was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of alrizomadlin plus pembrolizumab in patients with unresectable or metastatic melanoma or advanced solid tumors. Alrizomadlin is currently being investigated for treatment of patients with cutaneous melanoma that progressed on prior immunotherapy.

- As of December 12, 2022, a total of 31 patients with cutaneous melanoma that had progressed on PD-1/PD-L1 immunotherapy were enrolled in the study. The median (range) age of these patients was 65 (27-84) years, 21 (67.7%) of the patients were male, and 10 (32.3%) were female. Alrizomadlin 150 mg was administered every other day (QOD) for 2 consecutive weeks, with 1 week off, in 21-day cycles. Pembrolizumab 200 mg was administered intravenously on day 1 of the treatment cycles.

- Efficacy Results: In 26 efficacy-evaluable patients, 2 achieved CR, and 4 achieved PR, resulting in a confirmed ORR (ORR=CR+PR) of 23.1%. The initial analysis indicated that the ORR observed in patients whose disease had failed IO treatment was primarily attributable to the alrizomadlin plus pembrolizumab regimen, not the delayed effect of prior immunotherapy.

- Safety Results: A total of 30 (96.8%) patients reported TRAEs. The most frequent TRAEs (>10%) included nausea (71%), vomiting (38.7%), fatigue (35.5%), thrombocytopenia (32.3%), diarrhea (25.8%), neutropenia (19.4%), decreased appetite (16.1%), and decreased leukocyte count (12.9%). A total of 4 (12.9%) patients reported serious TRAEs, including anemia, thrombocytopenia, deep vein thrombosis, joint effusion, pulmonary embolism, and vomiting.

- Conclusions: Alrizomadlin combined with pembrolizumab is well tolerated and demonstrates clinical efficacy in patients with cutaneous melanoma that had failed IO drugs.

Appendix: The four posters on Ascentage Pharma's four lead drug candidates, including alrizomadlin, presented at this year's ASCO Annual Meeting.

References：

^[1].  Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.

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 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, has been granted Priority Review Designations and Breakthrough Therapy Designations (BTDs) 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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