At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Ibrahim Aldoss, MD, City of Hope National Medical Center, Duarte, California, shared results from the pivotal Augment-101 phase 2 study on the value of revumenib monotherapy among patients with relapsed/refractory (R/R) heavily pretreated histone-lysine N-methyltransferase 2A (KMT2A)-rearranged (KMT2Ar) acute leukemia. 

Revumenib demonstrated clinically meaningful results in a heavily pretreated KMT2Ar population, including a high overall response rate and rate of measurable residual disease negativity, according to Aldoss and coauthors. 

Transcript:

I am Dr Ibrahim Aldoss from City of Hope, Department of Leukemia and Hematopoietic Stem Cell Transplantation from Duarte, California. I’ll be sharing our results from the ASH 2023 Congress for the Augment-101 phase 2 study. 

KMT2A rearranged disease accounts for 10% of all acute leukemias and presents as myeloid or lymphoid leukemia, and can be seen in children and adults as well. It's a disease with unmet therapeutic needs. Frequently, patients relapse after standard chemotherapy and stem cell transplant. For patients with relapsed disease, the long-term outcomes and overall response to salvage therapy [are] low. Currently, there is no approved target therapy for KMT2A rearranged disease. Revumenib is a small molecule inhibitor of the KMT2A, a mini-interaction, and currently being tested in for KMT2A rearranged as well as [nucleophosmin 1] (NPM1) mutated acute leukemia. In [a] phase 1 study, it shows a manageable safety profile and encouraging activity. 

The Augment-101 phase 2 study is a multicenter study with the primary endpoint of [complete response + complete response with partial hematologic recovery] (CR+CRh) using single agent review enabled, recommended phase 2 dosing, and included both children and adults.

The study included a pre-specified interim analysis. Once the first 57 patients with confirmed mutation, they have an adequate follow-up. For patients enrolled in the Augment-101 phase 2 study, [almost a quarter] of the patients were children, and the majority [had] AML. These were heavily pretreated patients where almost half of the patients had 3 or [more] prior lines of therapy. Almost half of them had prior transplants. The majority had venetoclax before treatment in the study. With a median follow-up of 6 months, the overall response rate for single-agent revumenib was 63%. The study made the primary efficacy in point with CR+CRh rate of 23%, exceeding the 10%. 

The majority of responders were MRD-negative. The median response for patients achieving CR+CRh was 6 months, now close to 40% of responders. Almost close to 40% of responders were able to undergo curative allogeneic stem cell transplant, and half of transplanted patients were able to receive revumenib as a maintenance therapy. Afterward, toxicity was manageable with a low rate of drug discontinuation and dose reduction because of treatment-related adverse events. 

With that, the Augment-101 study shows that revumenib as single agent is safe and effective in children and adults with relapsed/refractory KMT2A rearranged leukemia. It induced durable and deep remissions and allowed many of those patients to proceed with curative allogeneic stem cell transplants. The study stopped early after the interim analysis based on meeting the efficacy in point for the study.
 

Source: 

Aldoss I, Issa GC, Thirman M, 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. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract LBA-5