SUZHOU, China and ROCKVILLE, Md.—Ascentage Pharma has announced that the company was given clearance of their Investigational New Drug (IND) application by the U.S. Food & Drug Administration (FDA). This will allow the company to initiate its Phase 1b clinical trial of HQP1351, a novel drug candidate developed by Ascentage for the treatment of patients with tyrosine kinase inhibitors (TKI)-resistant chronic myeloid leukemia (CML) in the U.S.
HQP1351 is the sixth molecule to receive clearance of IND from the FDA for Ascentage Pharma. The company submitted data generated from over 100 subjects in the Phase 1 clinical trial in China to the FDA to support the IND application.
“Ascentage Pharma used the clinical data from its HQP1351 Phase1 clinical trial in China to support the U.S. IND application. This FDA agreed Phase 1b clinical trial design could significantly accelerate HQP1351’s global clinical development program. Drug-resistant CML represents significant unmet clinical need, and we hope that HQP1351 will soon benefit patients worldwide,” said Dr. Yifan Zhai, chief medical officer of Ascentage Pharma.
The planned clinical study is a bridging Phase 1b clinical trial with three dose cohorts (30mg, 40mg and 50mg), which is more efficient than the traditional 3+3 dose-escalation study, and thus expected to accelerate the progress of this clinical trial. The study is designed to evaluate the safety, tolerability and pharmacokinetic (PK) of HQP1351 in CML patients who are resistant or intolerant to at least second-line TKIs, and to confirm the recommended Phase 2 dose (RP2D).
This clinical study will be led by Hagop Kantarjian, M.D., chair of the Department of Leukemia at MD Anderson Cancer Center. Other prominent U.S. research centers and hospitals will also participate.
Ascentage Pharma has developed HQP1351, a kinase inhibitor, to address acquired drug resistance from Imatinib treatment. 20-30% of CML patients treated with the drug develop acquired resistance, thus representing a major challenge to the treatment of CML. HQP1351 is an oral third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation.
The drug candidate is currently in pivotal Phase 2 clinical trial, and is the first third-generation BCR-ABL inhibitor targeting drug-resistant CML in China. A New Drug Application submission is planned upon the successful completion of the pivotal Phase 2 clinical studies in China. The drug candidate has also entered a Phase 1 trial in patients with GIST in China.
The updated data from the HQP1351 Phase 1 study in China was accepted as an oral presentation at the 60th American Society of Hematology annual meeting in December 2018. The preliminary data showed that HQP1351 was effective in the treatment of first and second generation TKI-resistant CML, especially the highly resistant CML with T315I mutation, with improved safety profile compared to other agents in the same class. The results demonstrate HQP1351’s best-in-class potential for treating TKI-resistant CML.