Dr Jabbour on Bleximenib Monotherapy in KMT2A+ or NPM1+ R/R Acute Leukemia

“What we’ve shown so far is that treatment with bleximenib is well tolerated, [There was] no QTc prolongation, and grade 3/4 differentiation syndrome was only [reported] in 6.5% of patients [treated at the recommended phase 2 dose].”

Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses findings from the phase 1/2 cAMeLot-1 study (NCT04811560) evaluating bleximenib (JNJ-75276617) monotherapy in patients with relapsed/refractory acute leukemia harboring KMT2A rearrangements or NPM1 mutations.

The dose-escalation portion of the study examined multiple doses, and efficacy data presented at the 2024 ASH Annual Meeting focused on evaluable patients treated with bleximenib at 45 mg twice daily (n = 11), 90/100 mg twice daily (n = 21), and 150 mg twice daily (n = 20). The overall response rate was 36.4% in the 45-mg cohort, 47.6% in the 90/100-mg cohort, and 55.0% in the 150-mg cohort. Composite complete response (CR_ rates, incorporating CR with or without hematologic recovery, were 18.2%, 38.1%, and 40.0%, respectively. Median time to first response ranged from 1.0 to 1.5 months across cohorts. In the 90/100-mg cohort, 14.3% of patients proceeded to allogeneic stem cell transplant, Jabbour explains.

Further analysis based on genetic subtypes showed respective composite CR rates of 44.4% and 33.3% in patients with KMT2A rearrangements (n = 9) or NPM1 mutations (n = 12) treated at 90/100 mg of bleximenib. Median follow-up for all dosed patients (n = 146) was 6.5 months; the median duration of CR/CR with partial hematologic recovery was 6 months (95% CI, 1.9-not evaluable).

Bleximenib was well tolerated with a manageable safety profile. The 150-mg dose was associated with an increased rate of dose modifications and discontinuations. Grade 3 or higher neutropenia was also more common at the highest dose level.

Based on these results, the recommended phase 2 dose (RP2D) was determined to be 100 mg twice daily following a 50-mg, twice daily step-up dose for 14 days. Jabbour explains that the 100-mg dose level showed superior efficacy to the 45-mg dose. The efficacy of the 100-mg and 150-mg doses were similar, but the lower dose was considerably safer, he adds. The phase 2 portion of the cAMeLot-1 study is ongoing and will further evaluate the efficacy/safety of bleximenib monotherapy in this patient population.