On December 7, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported positive data from two pivotal Phase II clinical trials of HQP1351 (olverembatinib) in an oral presentation at the 62nd ASH (Free ASH Whitepaper) Annual Meeting (Press release, Ascentage Pharma, DEC 7, 2020, View Source [SID1234572378]). These results were presented by the principal investigator of the study, Qian Jiang, MD, Deputy Chief of the Hematology Department at Peking University People’s Hospital. Following oral presentations in 2018 and 2019, this is the third consecutive year in which clinical study results of HQP1351 were selected for oral presentation at the ASH (Free ASH Whitepaper) Annual Meetings, signifying the recognition of HQP1351’s safety and efficacy from the international hematology community.
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HQP1351 is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma for the treatment of patients with CML resistant to first- and second-generation TKIs, including those with the T315I mutation. Based on results from two pivotal Phase II trials, Ascentage Pharma submitted a New Drug Application (NDA) for HQP1351 for the treatment of patients with T315I-mutated CML in chronic-phase (CML-CP) or accelerated-phase (CML-AP) in China this year, and the NDA was subsequently granted Priority Review status.
At 12:30 PST, December 7, during the session "Chronic Myeloid Leukemia: Therapy: CML: New and Beyond", Dr. Qian Jiang delivered an oral presentation on results from the pivotal Phase II studies of HQP1351, in an address titled "Novel BCR-ABL1 Tyrosine Kinase Inhibitor (TKI) HQP1351 (Olverembatinib) Is Efficacious and Well Tolerated in Patients with T315I-Mutated Chronic Myeloid Leukemia (CML): Results of Pivotal (Phase II) Trials".
Highlights of the results:
Two pivotal Phase II trials of HQP1351 in patients with TKI-resistant and T315I-mutated CML-CP or CML-AP were conducted in China. Patients in the studies were administered HQP1351 at 40 mg once every other day (QOD).
As of the data cut-off date of March 23, 2020, pivotal Phase II study HQP1351-CC201 had enrolled 41 patients with CML-CP. Across a median follow-up of 7.9 months, the mean 3-month progression-free survival (PFS) was 100%, and the 6-month PFS was 96.7%. A total of 75.6% of evaluable patients achieved a major cytogenetic response (MCyR), including 65.9% with a complete cytogenetic response (CCyR) and 48.8% with a major molecular response (MMR).
As of the data cut-off date of February 11, 2020, pivotal Phase II study HQP1351-CC202 had enrolled 23 patients with CML-AP. Across a median follow-up of 8.2 months, the 3-month PFS was 100% and the 6-month PFS was 95.5%. A total of 78.3% of evaluable patients achieved a major hematologic response (MaHR), including 60.9% of patients with a complete hematologic response (CHR). A further 52.2% of patients achieved MCyR, including 39.1% with CCyR and 26.1% with MMR.
In study HQP1351-CC201, the most frequent treatment-related adverse event (TRAE) of Grade 3-4 was thrombocytopenia (48.8%), and there were no treatment-related deaths.
In study HQP1351-CC202, the most frequent TRAE of Grade 3-4 was also thrombocytopenia (52.2%).
Results from the two studies show that HQP1351 was efficacious and well tolerated in patients with T315I-mutated and TKI-resistant CML-AP or CML-CP, and the probability and depth of clinical response is expected to increase with prolonged treatment period.
"Once T315I mutation occurs in patients with CML-CP or CML-AP, first- and second-generation TKIs are no longer effective. Currently, there is no approved treatment for these TKI-resistant patients in China, thus representing an urgent unmet medical need," said presenting author Dr. Qian Jiang. "Results from these two pivotal Phase II studies of HQP1351 in patients with T315I-mutated and TKI-resistant CML-AP or CML-CP have demonstrated promising efficacy and tolerability profiles. We remain steadfast to continuing the clinical development of this China-developed innovative therapy and bringing it to patients as early as possible."
"We are very pleased that results from the Phase II studies of HQP1351, a third-generation BCR-ABL inhibitor, have demonstrated encouraging efficacy and tolerability," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "For this drug candidate to be selected for oral presentation at the ASH (Free ASH Whitepaper) annual meeting in three consecutive years really shows the recognition of HQP1351 as a potential treatment for CML from the international hematology community. The release of these results marks another major milestone for the development of HQP1351, following the NDA submission and Priority Review designation in China. We hope HQP1351 will soon obtain its market authorizations so that patients with drug-resistant CML in China and around the world may start benefiting from this novel therapy."
About HQP1351 (Olverembatinib)
Being developed by Ascentage Pharma, HQP1351 is a novel, orally active, potent third-generation BCR-ABL tyrosine kinase inhibitor (TKI) designed to effectively target a spectrum of BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). At present, a New Drug Application (NDA) for HQP1351 has been submitted in China, and the application was subsequently granted the Priority Review status. In July 2019, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study. In May 2020, the drug candidate was granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA. Furthermore, a Phase Ib trial of HQP1351 in patients with gastrointestinal stromal tumor (GIST) is also ongoing in China.