Ascentage Pharma's HQP1351 Receives FDA Clearance to Enter Ib Clinical Trial for TKI-Resistant Chronic Myeloid Leukemia

On July 22, 2019, Ascentage Pharma, a clinical-stage biopharmaceutical company dedicated to developing innovative drugs in the fields of oncology, hepatitis B, and age-related diseases, announced that it had received notification from the U.S. Food and Drug Administration (FDA) approving its investigational new drug HQP1351 to proceed directly into Phase Ib clinical trials for the treatment of chronic myeloid leukemia (CML) resistant to tyrosine kinase inhibitors (TKIs).

The application was rapidly approved within 30 days, marking the sixth new drug from Ascentage Pharma to receive clinical trial approval in the United States. It is understood that, based on extensive Phase I clinical data from over 100 subjects completed in China for HQP1351, the U.S. FDA has authorized the drug to proceed directly into Phase Ib. This Phase Ib study employs a parallel-group bridging trial design across three dose cohorts (30 mg, 40 mg, and 50 mg). Compared with the traditional 3+3 dose-escalation approach, this design is more streamlined and efficient, and is expected to significantly accelerate the progress of the product’s clinical development.

This Phase Ib study aims to characterize the pharmacokinetic (PK) profile of HQP1351 in US patients with chronic myeloid leukemia (CML) who are resistant or intolerant to at least two prior lines of tyrosine kinase inhibitor (TKI) therapy, to determine the recommended Phase II dose, and to evaluate the safety and tolerability of HQP1351 in this patient population. The study will be led by principal investigator Dr. Hagop Kantarjian, Director of the Leukemia Department at MD Anderson Cancer Center and a globally renowned expert in hematologic oncology, with participation from multiple prestigious research centers and hospitals in the field.

Despite the significant clinical benefits of imatinib in the treatment of chronic myeloid leukemia (CML), 20%–30% of patients experience disease progression or drug resistance, with acquired resistance becoming a major challenge in CML management. HQP1351 is an original Class 1 investigational new drug developed by Ascentage Pharma. It is an oral third-generation BCR-ABL tyrosine kinase inhibitor (TKI) that targets various BCR-ABL mutants, including those with the T315I mutation, for the treatment of CML patients who have developed resistance to TKIs. This agent is the first domestically developed third-generation BCR-ABL-targeted therapy for TKI-resistant CML in China. It is currently in pivotal Phase II clinical trials in China, and a New Drug Application (NDA) can be submitted upon completion of the Phase II trial.

Notably, the Phase I clinical trial of HQP1351 in China was selected for an oral presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) last year. The reported data demonstrated that HQP1351 exhibits robust efficacy in chronic myeloid leukemia (CML) patients resistant to first- and second-generation tyrosine kinase inhibitors (TKIs), particularly those with the highly resistant T315I mutation, while offering a superior safety profile compared to global counterparts. These findings suggest that HQP1351 has the potential to become a “Best-in-Class” therapeutic agent for the treatment of resistant CML, garnering significant attention from the industry.

Dr. Zhai Yifan, Chief Medical Officer of Ascentage Pharma, stated, “The approval of the U.S. clinical trial application for HQP1351 within 30 days, allowing direct entry into Phase Ib, signifies the FDA’s recognition of HQP1351 and the clinical data from China. This will significantly accelerate the global clinical development of HQP1351. Drug-resistant chronic myeloid leukemia (CML) remains an unmet clinical need, and we hope to bring benefits to patients worldwide as soon as possible.”

HQP1351 is an original Class 1 investigational new drug developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor that targets various BCR-ABL mutants, including those with the T315I mutation, for the treatment of patients with resistant chronic myeloid leukemia (CML). The dose-escalation Phase I clinical trial in patients with TKI-resistant CML has been completed in China, and a pivotal Phase II clinical trial has been initiated. Furthermore, a Phase I clinical trial in patients with gastrointestinal stromal tumors (GIST) has been launched in China.

Ascentage Pharma is a clinical-stage, innovation-driven biopharmaceutical company headquartered in China with a global reach, dedicated to developing novel therapeutics in the fields of oncology, hepatitis B, and age-related diseases. The company possesses a proprietary protein-protein interaction (PPI) targeted drug design platform. Ascentage Pharma’s R&D pipeline primarily focuses on inhibitors of key proteins in the apoptosis pathway, such as BCL-2, IAP, and MDM2-p53, to reactivate apoptotic programs in tumor cells, as well as second- and third-generation inhibitors targeting kinase mutations that emerge during cancer treatment. Currently, eight Class 1 new drugs developed by the company have entered Phase I/II clinical development in China, the United States, and Australia.