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

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.