Bleximenib Shows Promising Results in Advanced Acute Leukemia Trial with KMT2A and NPM1 Mutations
核心洞察
Phase 1/2 cAMeLot-1 (搜索) trial demonstrates bleximenib's efficacy with up to 55% overall response rate in relapsed/refractory acute leukemia (搜索) patients at various dose levels.
The 100mg twice-daily dose emerged as the recommended Phase 2 dose, showing optimal balance between efficacy and safety with 38.1% composite complete response rate.
Treatment demonstrated favorable tolerability with only 6.5% of patients experiencing grade 3/4 differentiation syndrome (搜索) at the recommended phase 2 dose.
The investigational drug bleximenib (JNJ-75276617) has demonstrated encouraging efficacy and safety results in patients with relapsed/refractory acute leukemia (搜索) harboring specific genetic mutations, according to new data from the phase 1/2 cAMeLot-1 (搜索) trial.
Dr. Elias Jabbour, professor at The University of Texas MD Anderson Cancer Center's Department of Leukemia, presented findings showing dose-dependent responses across multiple treatment cohorts. The study evaluated three dose levels: 45 mg, 90/100 mg, and 150 mg, all administered twice daily.
Efficacy Across Dose Cohorts
The highest overall response rate of 55.0% was observed in the 150 mg cohort, while the 90/100 mg and 45 mg cohorts achieved 47.6% and 36.4% respectively. Composite complete response rates, which included complete response with or without hematologic recovery, reached 40.0% in the 150 mg cohort, 38.1% in the 90/100 mg group, and 18.2% in the 45 mg cohort.
Patients typically showed rapid responses, with median time to first response ranging from 1.0 to 1.5 months across all cohorts. Notably, 14.3% of patients in the 90/100 mg cohort proceeded to allogeneic stem cell transplant.
Genetic Subtype Analysis
The study specifically examined outcomes in patients with KMT2A (搜索) rearrangements and NPM1 (搜索) mutations treated at the 90/100 mg dose level. Results showed composite complete response rates of 44.4% in patients with KMT2A rearrangements (n=9) and 33.3% in those with NPM1 mutations (n=12).
Safety Profile and Optimal Dosing
"Treatment with bleximenib is well tolerated," reported Dr. Jabbour, noting that only 6.5% of patients experienced grade 3/4 differentiation syndrome (搜索) at the recommended phase 2 dose. The study found no QTc prolongation, although the 150 mg dose showed increased rates of dose modifications and discontinuations, along with higher incidence of grade 3 or higher neutropenia (搜索).
With a median follow-up of 6.5 months across all 146 dosed patients, the median duration of complete response or complete response with partial hematologic recovery was 6 months (95% CI, 1.9-not evaluable).
Phase 2 Development
Based on the optimal efficacy-safety profile, researchers established 100 mg twice daily as the recommended phase 2 dose, following a 14-day step-up period at 50 mg twice daily. The ongoing phase 2 portion of the cAMeLot-1 (搜索) study continues to evaluate bleximenib monotherapy in this patient population.