Live from ESMO 2023 | Oral Report Featuring Latest Data of Pelcitoclax (APG-1252) Combined with Osimertinib Demonstrates Potential as a New Treatment Option for TP53-and EGFR-Mutant NSCLC

SUZHOU, China and ROCKVILLE, Md., Oct. 23, 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 the latest clinical data of its dual Bcl-2/Bcl-xL inhibitor, APG-1252 (pelcitoclax), combined with osimertinib for the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC) in a Mini Oral at the 2023 European Society of Medical Oncology (ESMO) Congress.

Developed by Ascentage Pharma, pelcitoclax is a potential best-in-class novel dual Bcl-2/Bcl-xL inhibitor that can restore the apoptosis of cancer cells by selectively inhibiting Bcl-2 and Bcl-xL proteins, thus delivering its therapeutic effects on a range of solid tumors and hematologic malignancies.

The clinical data presented at the ESMO Congress this year demonstrated promising therapeutic utility of pelcitoclax combined with osimertinib in patients with EGFR-mutant NSCLC. Those results show that among the 26 EGFR-tyrosine kinase inhibitor (TKI)-naïve patients, 21 partial responses (PRs) were observed, resulting in an objective response rate (ORR) of 80.8%; while among the 16 EGFR-TKI naïve patients with TP53 and EGFR-mutations, 14 PRs were observed, resulting in an ORR of 87.5%.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "Currently, there are many challenges in the treatment of NSCLC. Among them, TP53 and EGFR mutations can significantly affect the prognosis of patients with NSCLC, and there is no standard of care treatment for this subtype of NSCLC. At the ESMO 2023, we presented the latest clinical data that continued to suggest encouraging therapeutic potential of pelcitoclax combined with osimertinib in EGFR-TKI-naïve patients with TP53- and EGFR-mutant NSCLC.

In earlier studies, pelcitoclax combined with osimertinib demonstrated clinical potential for the treatment of patients with EGFR-mutant advanced NSCLC resistant to EGFR-TKIs. Adding to the body of evidence, updated data presented this year revealed clinical potential of the combination regimen in patients resistant to third-generation EGFR-TKIs. Moving forward, we will continue to fulfill our mission of addressing unmet clinical needs in China and around the world and expedite our clinical programs for the benefit of more patients."

Highlights of the data on pelcitoclax presented at the 2023 ESMO Congress are as follows:

Updated study results of pelcitoclax (APG-1252) combined with osimertinib in patients (pts) with EGFR-mutant non-small-cell lung cancer (NSCLC)

• Format: Mini Oral
• Abstract#: 5586
• Date and Time: October 22, 2023 (Sunday), 02:30 PM – 02:35 PM (Madrid Time) / October 22, 2023 (Sunday), 08:30 PM – 08:35 PM (Beijing Time)
• Category: NSCLC, metastatic
• Highlights
  • This open-label, multi-center, Phase Ib study being conducted in China was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of pelcitoclax in combination with osimertinib in patients with EGFR-mutant NSCLC.
  • As of April 21, 2023, 64 patients were enrolled with a median age of 56 years. To the 13 patients enrolled in the dose escalation phase, pelcitoclax was administered intravenously once weekly (QW) at 160 mg (n=6) and 240 mg (n=7); while osimertinib was orally administered once daily (QD) at 80 mg, in 21-day cycles. After establishing 160 mg as the recommended Phase II dose (RP2D) of pelcitoclax, the study enrolled another 51 patients into the dose-expansion phase that divided the 64 patients into 3 cohorts: Cohort 1 included patients with disease resistant to first-generation EGFR-TKIs (n=8), Cohort 2 included patients with disease resistant to third-generation EGFR-TKIs (n=29), Cohort 3 included patients whose disease was previously untreated with EGFR-TKIs (n=27).
  • Efficacy results: In the 26 efficacy-evaluable EGFR-TKI-naïve patients, 21 partial responses (PRs) were observed, resulting in an ORR of 80.8%. In the 16 EGFR-TKI- naïve patients with TP53 and EGFR mutations, 14 PRs were observed, resulting in an ORR of 87.5% and a median progress-free survival (mPFS) of 16.39 months (95%Cl, 8.11-NR). Furthermore, preliminary biomarker data from patients resistant to third-generation EGFR-TKIs suggest that the combination regimen can potentially prolong the PFS of patients with high Bcl-xL expressions.
  • Safety results: A total of 59 patients (92.2%) experienced treatment-emergent adverse events (TEAEs), of whom only 13 (20.3%) experienced grade≥3 AEs. The most common TEAEs included increased aspartate aminotransferase (68.8%) and alanine aminotransferase (64.1%), reduced platelet counts (43.8%), increased serum amylase (29.7%), and increased blood creatinine (28.1%).
  • Conclusions: According to the preliminary results, pelcitoclax in combination with osimertinib showed favorable tolerability in patients with EGFR-mutant NSCLC, and the potential for improving the prognosis of EGFR-TKI-naïve patients with TP53- and EGFR-mutant NSCLC. In patients resistant to third-generation EGFR-TKIs, those with higher Bcl-xL expressions achieved better responses. These encouraging findings warrant further clinical investigations.

(Pelcitoclax is an investigational drug that has not been approved for any indication anywhere in the world.)

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 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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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