Syndax Releases Revuforj Clinical Trial Data
Syndax announced that data from the Phase 1/2 SAVE trial of an all-oral regimen of Revuforj, decitabine/cedazuridine, and venetoclax in relapsed or refractory NPM1 mutated, KMT2A-rearranged, or NUP98-rearranged acute myeloid leukemia were published in the Journal of Clinical Oncology and simultaneously presented at the European Hematology Association 2026 Congress in Stockholm, Sweden. Revuforj is the first and only menin inhibitor that is FDA approved for patients one year and older with R/R AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options or R/R acute leukemia with a KMT2A translocation as determined by an FDA-authorized test. The publication reports results from the R/R cohort of patients in the Phase 1/2, single-center, open-label SAVE trial. The primary endpoint of Phase 1 was the recommended Phase 2 dose of revumenib in combination therapy, which was identified as dose level 1. The primary endpoint of Phase 2 was the composite complete remission rate. As of January, 42 patients with R/R AML were enrolled in the SAVE trial, including five adolescents. 38% had NPM1m, 40% had KMT2Ar, and 21% had NUP98r. The median age was 40 years. Patients were heavily pretreated, with a median of two prior lines of therapy; 52% had received prior venetoclax and 33% a prior hematopoietic stem cell transplant. The overall response rate was 88%, the CRc rate was 71%, and the complete remission plus complete remission with partial hematological recovery rate was 60% for the entire population. Response rates were similar across genotypes, including patients with NPM1m, KMT2Ar, or NUP98r. Overall, 45% of patients proceeded to HSCT following treatment with the regimen, including 38% of NPM1m patients, 65% of KMT2Ar patients, and 22% of NUP98r patients. Of the 19 patients that proceeded to HSCT, 63% resumed revumenib after HSCT. The rates of measurable residual disease negativity by flow cytometry were 68% among evaluable responders, 80% among those with CRc, and 80% among those with CR/CRh. Among evaluable patients with CRc, 67% were MRD negative by NPM1 NGS, with the vast majority of those patients below the limit of detection of the assay, highlighting the depth of MRD clearance. With a median follow-up of 22 months, the median duration of response among patients with CR/CRh was 10.5 months for the entire cohort, 10.7 months among NPM1m patients, not reached among KMT2Ar patients, and 5.9 months among NUP98r patients. The observed 1-year overall survival rate was 56% for the entire cohort, 63% among NPM1m patients, 47% among KMT2Ar patients, and 67% among NUP98r patients. Median OS after HSCT was not reached. Patients who were MRD negative by flow cytometry had a longer median duration of response and OS compared to those who were MRD positive. Notably, clinical activity was observed among patients with prior exposure to venetoclax, a population in whom outcomes are typically poor, with a historical estimated median survival of 2.4 months. In this trial, the CR/CRh rate was 50% in patients with venetoclax exposure versus 70% in those without. The median OS observed was similar between the two groups, based on a Kaplan-Meier estimate. This observation supports a potential biologic synergy between BCL2 inhibition and menin inhibition and the possibility that menin inhibition may restore sensitivity to BCL2 inhibition after resistance has developed. Revumenib was generally well-tolerated in combination with decitabine/cedazuridine and venetoclax. The most common treatment-emergent adverse events included elevations in aspartate aminotransferase or alanine aminotransferase, nausea, and vomiting. The most common Grade 3 TEAEs were febrile neutropenia, lung infection, thrombocytopenia, and elevations in aspartate aminotransferase or alanine aminotransferase. Rates of Grade 3 differentiation syndrome and QTc prolongation were both low.
