B08 | Updated Results and Longer Follow-up From the Augment-101 Phase 2 Study of Revumenib in All Patients With Relapsed or Refractory Kmt2ar Acute Leukemia
Year: 2025
Type: article
Abstract: Background: Revumenib (rev), an oral, potent, selective menin inhibitor, met the prespecified stopping rules for efficacy in patients (pts) with R/R KMT2A-rearranged (r) acute leukemia (AL) in the phase 2 interim analysis (IA) of AUGMENT-101. Here we report longer follow-up (f/u) and a larger data set. Methods: Pts aged ≥30d with R/R KMT2Ar AL received rev 163 mg (95 mg/m2 if body weight <40kg) q12h with a strong CYP3A4 inhibitor in 28-d cycles until lack of morphological leukemia-free state (MLFS) after 4 cycles, disease progression, or unacceptable AEs. Primary objectives were safety, tolerability, and rate of complete remission (CR) or CR with partial hematologic recovery (CR+CRh). Key secondary endpoints were rate of composite CR (CRc [CR+CRh+CRp+CRi), ORR (CRc+MLFS+PR), and duration of response (DOR). The efficacy population included pts with centrally confirmed KMT2Ar AL and ≥5% baseline BM blasts. MRD was assessed locally by flow cytometry or PCR. Results: In this analysis (data cutoff: 29 Feb 2024), the updated median duration of CR+CRh in 13 responders from the IA was 13.0 mo (95% CI, 3.4 mo-NR); 5 remained in f/u with no relapse or death, 1 additional pt relapsed. 116 pts received ≥1 dose of rev. Median age was 35.5 y (range, 0.6-75.0y); 28 (24%) were <18 y, 14 (12%) were ≥65y. 95 pts (82%) had AML, 67 (58%) were female, and 18 (16%) were non-White. Pts were heavily pretreated: 51 (44%) had ≥3 prior therapies, 73 (63%) had prior venetoclax, 59 (51%) had prior alloHSCT. In the efficacy population (n=97), 22 pts (23% [95% CI, 15-32%]) achieved CR+CRh, with a median DOR of 6.4mo (95% CI, 1.9 mo-NR). CRc was 42% (95% CI, 32-53%); ORR was 64% (95% CI, 54-73%). 11/18 (61%) CR+CRh responders and 21/36 (58%) CRc responders with available MRD status achieved MRD negativity. 21/62 pts (34%) who achieved ORR proceeded to alloHSCT; 9 resumed rev post alloHSCT. In the safety population (N=116), 106 pts (91%) had a grade (gr) ≥3 TEAE. The most common gr ≥3 TEAEs were febrile neutropenia (45 [39%]), anemia (23 [20%]), platelet count decreased (19 [16%]), differentiation syndrome (17 [15%]; 1 gr 4, no gr 5), neutrophil count decreased (17 [15%]), WBC count decreased (17 [15%]), sepsis (16 [14%]), and QTc prolongation (15 [13%]; all gr 3). 16 pts (14%) discontinued treatment due to a TEAE; 19 (16%) had a gr 5 TEAE. Conclusions: Rev demonstrated clinically meaningful responses in heavily pretreated pts with R/R KMT2Ar AL; the safety profile is manageable.
Authors: C. Papayannidis, I. Aldoss, G. Issa, J. Blachly, M. Thirman, G. Mannis, M. Arellano, J. Dipersio, E. Traer, M. Zwaan, N. Shukla, B. Cuglievan, C. Grove, M. Greenwood, C. Mcmahon, A. Perl, R. Stone, D. Dickens, M. Heiblig, A. Žučenka, P. Montesinos, I. Mantzaris, T. Kovacsovics, P. Shami, L. Yu, R. Bagley, A. Smith, E. Stein
Institutions: Istituto di Ematologia di Bologna, City Of Hope National Medical Center, The University of Texas MD Anderson Cancer Center, The Ohio State University, University of Chicago, Stanford Medicine, Stanford University, Winship Cancer Institute, Washington University in St. Louis, Oregon Health & Science University, OHSU Knight Cancer Institute, Princess Máxima Center, Erasmus MC - Sophia Children’s Hospital, Memorial Sloan Kettering Cancer Center, The University of Western Australia, Sir Charles Gairdner Hospital, The University of Sydney, Royal North Shore Hospital, University of Colorado Anschutz, University of Colorado Denver, University of Pennsylvania, Dana-Farber Cancer Institute, University of Iowa Stead Family Children’s Hospital, Hôpital Lyon Sud, Vilnius University, Hospital Universitari i Politècnic La Fe, Montefiore Medical Center, Montefiore Einstein Comprehensive Cancer Center, City of Hope, Huntsman Cancer Institute, Syndax Pharmaceuticals (United States)
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122574
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