SUJOU, China, and ROCKVILLE, MD., September 8, 2021 / PRNewswire / – Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in the development of novel therapies for cancer, chronic hepatitis B (CHB) and age-related diseases, announced today Phase Ib results of the double Bcl-2 / Bcl-xL inhibitor, APG-1252 (pelcitoclax), in combination with osimertinib in patients with non-small cell lung cancer (NSCLC) resistant to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKI), in a mini oral session at the 2021 World Lung Cancer Conference (WCLC). The data were presented by Pr. Li Zhang, the principal investigator of the Sun-Yat Sen University Cancer Center study.
Organized by the International Association for the Study of Lung Cancer (IASLC), the World Lung Cancer Conference (WCLC) is the world’s largest multidisciplinary oncology event dedicated to lung cancer and other thoracic cancers, with an emphasis on the most advanced research. and clinical advances in the field. The results presented by Ascentage Pharma at this year’s WCLC are from a single-arm, phase Ib, multi-center dose escalation and dose extension study designed to assess pharmacokinetics (PK), safety and Preliminary efficacy of pelcitoclax in combination with osimertinib in patients with EGFR mutant NSCLC.
Developed by Ascentage Pharma, pelcitoclax is a new small molecule drug candidate that restores apoptosis by selectively simultaneously inhibiting the Bcl-2 and Bcl-xL proteins. In preclinical studies, pelcitoclax in combination with osimertinib demonstrated synergistic antitumor effects in animal models of EGFR mutant NSCLC that were sensitive or resistant to osimertinib. Therefore, pelcitoclax in combination with osimertinib has the potential to provide a new treatment option.
Highlights from the data presented in a mini oral session at this year’s WCLC:
Phase 1b Study of Pelcitoclax (APG-1252) in Combination with Osimertinib in Patients with EGFR-Resistant NSCLC TKI
Track: New therapies and targeted therapies
Time: 10:05 a.m. – 10:10 a.m., September 8, 2021 mountain time / 00:05 – 00:10, September 9, 2021, Beijing time
This multicenter, single-arm phase Ib study of pelcitoclax in combination with osimertinib in patients with advanced EGFR mutant NSCLC included a dose escalation phase and a dose expansion phase. dose. Pelcitoclax was administered at 160 mg or 240 mg by IV infusion once weekly, and osimertinib was administered orally at 80 mg per day (QD). Dose escalation primarily assessed the safety and tolerability of the combination regimen in patients who progressed on previous treatments with TKI EGFR, and determined the maximum tolerated dose (MTD) and / or the recommended phase dose. II (RP2D) of pelcitoclax. The dose extension consisted of two arms: 1) Patients with third generation EGFR TKI-resistant NSCLC; 2) Patients with osimertinib naive NSCLC. Each arm planned to enroll 20 patients.
From June 24, 2021, 56 patients were included in the study. 33 of them were included in the dose escalation and dose extension arm 1. These patients had received a median of 4 (range: 1-10) lines of prior treatment, 87.9% had received chemotherapy regimens, 75.8% had been treated with osimertinib, and 63.6% had brain metastases at the time of enrollment. The 23 patients included in arm 2 had received a median of 0 (range: 0-2) lines of previous treatment, 8.7% had received chemotherapy, 17.4% had been treated with tyrosine kinase inhibitors ( TKI) of the first generation and 30.4% had brain metastases at the time of enrollment.
At dose escalation, 1 partial response (PR) was observed in the 11 evaluable patients. In arm 1 of the dose extension phase, 3 PR (2 were resistant to osimertinib) and 13 stable diseases (SD) were observed in the 20 evaluable patients, with an objective response rate (ORR) of 15% and a disease control rate (DCR) of 80%. In arm 2 of the dose extension phase, 13 PR and 8 SD were observed in the 22 evaluable patients, including 3 patients harboring the EGFR Exon 20 insertion, with an ORR of 59.1% and a DCR of 95.5%.
In escalating dose, one case of dose-limiting toxicity (DLT) of grade 4 thrombocytopenia was observed at 240 mg; while no grade 3 or greater thrombocytopenia was observed at 160 mg, and the increase in alanine aminotransferase (ALT) and aspartate aminotransferase (ASAT) also occurred at a much higher rate low than 240 mg. Thus, pelcitoclax 160 mg per week plus osimertinib 80 mg once daily was chosen as RP2D. The most common treatment-related adverse events included transient thrombocytopenia, increased ASAT, increased ALT, increased amylase, increased blood creatinine, decreased white blood cells, anemia and a rash.
Conclusion: Pelcitoclax in combination with osimertinib was safe and well tolerated. Preliminary synergistic anti-tumor effects have been observed in some patients with osimertinib-resistant NSCLC. In patients who received osimertinib for the first time, pelcitoclax demonstrated preliminary synergistic antitumor effects with osimertinib similar to those of navitoclax.
Teacher. Li Zhang, principal investigator of the Sun-Yat Sen University Cancer Center study, said: “Although osimertinib is currently the preferred first-line treatment for patients with EGFR mutant NSCLC, it There is still no effective treatment for patients resistant to osimertinib. Our data presented at this year’s WCLC demonstrated the synergistic anti-tumor effects of pelcitoclax and osimertinib in some osimertinib-resistant patients, indicating the potential as a new clinical strategy that could address this unmet medical need. perform additional biomarker analysis with the aim of enriching the patient population responding to this regimen. “
Dr. Yifan Zhai, Medical Director of Ascentage Pharma, commented: “There is currently a huge unmet medical need in patients with NSCLC, especially in the EGFR TKI resistant subgroup who are in desperate need of treatment options. effective. These results were presented to WCLC this year. demonstrated the therapeutic potential of pelcitoclax and osimertinib in patients with EGFR TKI-resistant NSCLC, and therefore warranted further clinical investigation. We will continue this clinical development program which will hopefully provide a new treatment option for patients in need.
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a global biopharmaceutical company engaged in the development of new therapies against cancer, chronic hepatitis B and age-related diseases. At October 28, 2019, Ascentage Pharma has been listed on the Main Board of the Hong Kong Stock Exchange Limited with the stock code: 6855.HK.
Ascentage Pharma is focused on the development of therapies that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of eight clinical drug candidates, including new, very potent inhibitors of Bcl-2 and double Bcl-2 / Bcl-xL, as well as candidates for the IAP and MDM2-p53 pathways, and the new generation tyrosine. kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting the three known classes of key regulators of apoptosis. The company is conducting more than 40 Phase I / II clinical trials in the United States, Australia, Europe, and China. Ascentage Pharma has been nominated for several 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. HQP1351, the Company’s lead drug candidate developed for the treatment of drug-resistant chronic myelogenous leukemia (CML), has received Orphan Drug Designation (ODD) and Expedited Designation (FTD) from the US FDA. A New Drug Application (NDA) for HQP1351 was submitted and subsequently granted Priority Review status and Breakthrough Therapy (BTD) designation by the Center for Drug Evaluation (CDE) in China. To date, Ascentage Pharma has obtained a total of 12 US FDA SDGs for 4 of the Company’s investigational drug candidates.
Leveraging its strong R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and has entered into global partnerships with many renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institut, MSD, and AstraZeneca. The company has assembled a talented team with global experience in innovative drug discovery and development, and is building its world-class commercial manufacturing and sales and marketing teams. Ascentage Pharma aims to continuously strengthen its R&D capabilities and accelerate its clinical development programs to fulfill its mission of “responding to unmet clinical needs by China and around the world ”for the benefit of more patients.
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