AUGMENT-101: Excellent results for revumenib in R/R KMT2Ar leukaemia

Revumenib appeared to be safe and efficacious in participants with relapsed or refractory (R/R) KMT2A gene rearranged (KMT2Ar) acute leukaemia, results of the phase 2 AUGMENT-101 trial showed.

Most patients with KMT2Ar acute leukaemia relapse after transplantation and there are no approved therapies for patients with this condition. Also, the menin-KMT2A interaction is an important driver of leukaemogenesis [1].

In the phase 2 AUGMENT-101 trial (NCT04065399), the oral menin inhibitor revumenib was assessed in paediatric and adult participants with R/R KMT2Ar acute leukaemia for efficacy (n=57) and safety (n=94) [2]. Approximately a quarter of the participants were below 18 years of age. Enrolled participants received revumenib (163 mg or 95 mg/m² in case a participant’s body weight was below 40 kg) every 12 hours plus a strong CYP3A4 inhibitor in 28-day cycles. The primary endpoint was the complete remission (CR) rate plus CR with partial haematological recovery (CRh). The key findings were presented by Dr Ibrahim Aldoss (City of Hope National Medical Center, CA, USA).

The overall response rate was 63% (see Table) and after a follow-up of 6.1 months, 13 participants achieved CR plus CRh, meeting the primary endpoint threshold of 10% (22.8%; 95% CI 12.7–35.8; P=0.0036). The composite CRc rate (defined as CR+CRh+CR with incomplete platelet recovery+CR with incomplete count recovery) was 44% and 68% of participants who achieved CRc reached minimal residual disease (MRD)-negativity.

Table: Best response results from the AUGMENT-101 trial [2]



^bIncludes patients without post-baseline disease assessment

The most frequently observed grade ≥3 treatment-emergent adverse events were differentiation syndrome (16.0%), febrile neutropenia (37.2%), and QTc prolongation (13.8%). “No participants discontinued due to differentiation syndrome, QTc prolongation, or cytopenia,” added Dr Aldoss.

“Based on these data, a new drug application for KMT2Ar leukaemia has been initiated under the FDA real-time oncology review programme,” Dr Aldoss announced in his talk.

1. Issa GC, et al. Blood Cancer J. 2021;11(9):162.
2. Aldoss I, et al. Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal Augment-101 Phase 2 Study. Abstract LBA-5, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

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Posted on 7 February 20247 February 2024