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4950 Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
adult, drug development, pediatric, Diseases, Therapies, Adverse Events, Lymphoid Malignancies, Study Population, Human, Minimal Residual Disease
Monday, December 11, 2023, 6:00 PM-8:00 PM

Andrius Žučenka, MD1, Ghayas C. Issa2, Martha Arellano3, Sajad Khazal2, Nandita Khera, MD4, Wendy Stock, MD5, Branko Cuglievan2, Yu Gu6*, Huy Van Nguyen6*, Angela R. Smith7* and Eytan M. Stein8

1Hematology and Oncology Department, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
2The University of Texas MD Anderson Cancer Center, Houston, TX
3Emory University School of Medicine, Atlanta, GA
4Mayo Clinic, Phoenix, AZ
5University of Chicago Medicine, Chicago, IL
6Syndax Pharmaceuticals, Inc., Waltham, MA
7Syndax Pharmaceuticals, Inc, Waltham, MA
8Memorial Sloan Kettering Cancer Center, New York, NY

Background: The potent and selective oral menin–histone-lysine N-methyltransferase 2A (KMT2A) inhibitor revumenib (SNDX-5613) induced complete remissions with clearance of residual disease in acute leukemias refractory to multiple previous lines of therapy (Nature. 2023;615:920-924). Here we report outcomes following the resumption of revumenib after hematopoietic stem cell transplant (HSCT).

Methods: Patients aged ≥30 days with relapsed or refractory (R/R) acute leukemias with genetic alterations associated with HOXA overexpression, including KMT2A-rearranged (KMT2Ar) or nucleophosmin 1 (NPM1)-mutated leukemias, were enrolled in the AUGMENT-101 phase 1/2, multicenter, open-label, dose-escalation study (NCT04065399). Patients received revumenib every 12 hours (q12h) in 28-day continuous cycles. Patients who achieved a complete response (composite definition [CRc]), morphological leukemia-free state, or partial response could undergo HSCT without leaving the study. Revumenib was stopped before the HSCT conditioning regimen but, per a protocol amendment, could be resumed after HSCT if the patient was in CRc. Measurable residual disease (MRD) was assessed using multiparameter flow cytometry and/or polymerase chain reaction.

Results: Between November 5, 2019, and June 28, 2023, a total of 131 phase 1 patients were enrolled and treated in the AUGMENT-101 study. Nine patients with acute myeloid leukemia (AML) from the AUGMENT-101 study resumed revumenib (8 after transplant and 1 after a stem cell boost [Table 1]). Seven patients had KMT2Ar and 1 patient each had nucleoporin 98 rearranged (NUP98r) and mutated NPM1. Revumenib was resumed 59 to 180 days after HSCT (Table 2). Dose was reduced for 4 of 9 patients to mitigate adverse events of thrombocytopenia (n=3) and leg pain (n=1), and revumenib was discontinued in 4 of 9 patients because of progressive disease (n=2), cytopenias (n=1), and not reported (n=1). Revumenib duration of treatment (DOT) in the maintenance setting at the time of this analysis ranged from 23 to 588 days, with treatment ongoing for 5 of the 9 patients. CRc was maintained in 6 of 9 patients after HSCT and maintenance revumenib. One patient with reported MRD after HSCT converted to MRD-negative status following initiation of revumenib maintenance therapy. Overall, MRD-negative remissions were maintained in 5 patients as of the data cut off.

Conclusions: With 3 patients on revumenib maintenance therapy for more than a year, long-term responses, including conversion to MRD-negative status, were seen in these heavily pretreated patients with AML. Resuming revumenib post HSCT had a tolerable safety profile consistent with that previously reported for the AUGMENT-101 study.

Disclosures: Žučenka: Abbvie: Consultancy, Honoraria, Other: Travel Expenses; Astellas: Consultancy, Honoraria; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel Expenses; Jannsen: Consultancy, Honoraria, Other: Travel Expenses; Takeda: Other: Travel expenses. Issa: Novartis: Consultancy, Research Funding; NuProbe: Consultancy, Research Funding; Merck: Research Funding; Kura Oncology: Consultancy, Research Funding; Syndax: Consultancy, Research Funding; Celgene: Research Funding; Astex: Research Funding; Abbvie: Consultancy; Cullinan Oncology: Research Funding. Khera: Incyte: Honoraria. Stock: Glaxo Smith Kline: Consultancy; Servier: Other: Data Safety Monitoring Board/Advisory Board; Newave: Honoraria; Kite: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria; Kura: Research Funding; Amgen: Honoraria. Gu: Syndax Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Nguyen: Syndax Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Smith: Syndax Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Stein: Bristol Myers Squib: Consultancy, Research Funding; Servier: Consultancy; Abbvie: Consultancy; CTI Biopharma: Consultancy; PinotBio: Consultancy; Neoleukin: Consultancy; Foghorn: Consultancy; Janssen: Consultancy; Agios: Consultancy; Jazz: Consultancy; Menarini: Consultancy; Genentech: Consultancy; Genesis: Consultancy; Gilead: Consultancy; Syndax: Consultancy; OnCusp: Consultancy; Calithera: Consultancy; Daiichi: Consultancy; Aptose: Consultancy; Syros: Consultancy; Eisai: Research Funding; Novartis: Consultancy; Astellas: Consultancy; Ono Pharma: Consultancy; Blueprint: Consultancy.

*signifies non-member of ASH