Ascentage Pharma presented new clinical data on olverembatinib (HQP1351) at the 66th American Society of Hematology (ASH) Annual Meeting, highlighting its potential as a second-line therapy for patients with chronic-phase chronic myeloid leukemia (CP-CML) who do not have the T315I mutation. The oral presentation featured the first dataset of olverembatinib in this setting, indicating promising responses and a favorable safety profile, especially in patients who previously failed second-generation tyrosine kinase inhibitors (TKIs).
The single-arm, multicenter, open-label study enrolled 43 patients with non-T315I-mutant CP-CML who were resistant or intolerant to one prior line of TKIs. Patients received 40 mg of oral olverembatinib every other day. The primary objective was to evaluate the efficacy and safety of olverembatinib in this patient population.
Efficacy Outcomes
As of the data cutoff on November 15, 2024, 74.1% of patients (20/27) achieved a complete cytogenetic response (CCyR), and 40.6% (13/32) achieved a major molecular response (MMR). Notably, the CCyR and MMR rates improved over time, with rates at the end of Cycles 6, 9, 12, and 18 demonstrating a consistent increase in efficacy. Specifically, in the 33 efficacy-evaluable patients, 24 had been pretreated with second-generation TKIs as first-line treatment, of whom 78.9% (15/19) achieved CCyR, and 43.5% (10/23) achieved MMR. For the 9 patients pretreated with imatinib, 50.0% achieved CCyR (4/8) and 33.3% achieved MMR (3/9).
Safety Profile
The median treatment duration was 16.0 months (range: 2-18 months). The majority of patients (95.3%) experienced any-grade treatment-related adverse events (TRAEs), with 48.8% experiencing grade ≥ 3 TRAEs. Common non-hematologic TRAEs included skin hyperpigmentation (51.2%), hyperuricemia (30.2%), and increased creatine phosphokinase (25.6%), most of which were grade 1 or 2. Grade ≥ 3 hematologic toxicities included decreased platelet count (46.5%), neutropenia (25.6%), and anemia (9.3%). Importantly, no arterial occlusive events (AOEs) or venous thromboembolisms (VTEs) were reported during the study. Olverembatinib-related serious adverse events (SAEs) included decreased platelet count (7.0%), anemia, and elevated ALT (2.3% each). No deaths were reported.
Clinical Significance
"Among patients with CP-CML, it is a common situation in which patients need to switch to another therapy after failing the first-line treatment with TKIs, and the efficacy of first- and second-generation TKIs often falls short of the desired outcome," said Professor Weiming Li, the study's principal investigator. "Therefore, patients have the desperate need for more second-line therapies that can offer higher efficacy. These data showed that, olverembatinib as a second-line treatment offers promising responses and potential clinical benefits... suggesting that olverembatinib can potentially provide a new strategy for the second-line treatment of patients with CML."
These findings suggest that olverembatinib could provide a valuable second-line treatment option for CP-CML patients, particularly those who have failed on second-generation TKIs. Ascentage Pharma plans to continue global clinical development of olverembatinib to address unmet clinical needs in CML and other malignancies.
