The investigational drug bleximenib (JNJ-75276617) has demonstrated encouraging efficacy and safety results in patients with relapsed/refractory acute leukemia harboring specific genetic mutations, according to new data from the phase 1/2 cAMeLot-1 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 rearrangements and NPM1 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 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.
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 study continues to evaluate bleximenib monotherapy in this patient population.
