A phase 2 study of olutasidenib in relapsed/refractory acute myeloid leukemia: Outcomes by number of prior treatment regimens.

6545 Background: A subset of patients (7-14%) with acute myeloid leukemia (AML) have mutations in the isocitrate dehydrogenase 1 gene (m IDH1 ). Olutasidenib (OLU), a selective, potent, oral inhibitor of mIDH1, is approved for treatment of relapsed/refractory (R/R) m IDH1 AML. Results from the phase 2 pivotal cohort (NCT02719574) demonstrated clinical efficacy and tolerability of OLU, with a complete remission/complete remission with partial hematological recovery (CR/CRh) rate of 35% for a median duration of 25.9 months. Here we evaluated the efficacy and safety of OLU in patients with R/R AML grouped by the number of prior regimens. Methods: The pivotal cohort of the phase 2 study assessed OLU 150 mg BID in adult patients and included efficacy endpoints of CR/CRh, overall response rate (ORR), duration of response (DOR), and overall survival (OS). This post hoc analysis evaluated outcomes based on when patients received OLU: after 1-2 or ≥3 prior lines of therapy. Results: There were 147 patients in the efficacy evaluable analysis set (1-2 prior regimens, n=93; ≥3 prior regimens, n=54). Median age was 72 years in patients with 1-2 prior regimens and 66.5 years in those with ≥3 prior regimens. Forty-three percent and 33% of patients had prior treatment with a hypomethylating agent, and 11% and 4% received prior venetoclax therapy (1-2 and ≥3 prior regimens groups, respectively). In patients with ≥3 prior regimens, 31% had prior hematopoietic stem cell transplantation vs none in those with 1-2 prior regimens. Those in the 1-2 prior regimens group had a higher ORR and CR/CRh rate and longer median OS, with a larger percentage of patients achieving CR, than those in the ≥3 prior regimens group (Table 1). All patients experienced ≥1 treatment-emergent adverse event (TEAE). Serious TEAEs were reported in 73% (68/93) and 77.8% (42/54) of patients in the 1-2 and ≥3 prior regimens groups, respectively, and TEAEs ≥grade 3 occurred in 89.2% (83/93) and 90.7% (49/54). The most common TEAEs included nausea, decreased red blood cell count, and fatigue. No new safety signals were identified. Conclusions: Higher response rates (including CR and CRh) and greater survival were observed in patients receiving OLU following 1-2 versus ≥3 prior treatment regimens, providing rationale for initiating OLU earlier in the R/R treatment paradigm. Clinical trial information: NCT02719574 . Efficacy of OLU stratified by number of prior regimens. 1-2 Prior Regimensn=93 ≥3 Prior Regimensn=54 ORR, n (%); 95% CI 50 (54); 43.1, 64.2 21 (39); 25.9, 53.1 DOR, median months (95% CI) 14.8 (7.4, 25.9) 16.6 (5.8, NR) CR rate, n (%); 95% CI 35 (38); (27.8, 48.3) 12 (22); (12.0, 35.6) DOR, median months (95% CI) 21.3 (12.0, NR) NR (8.7, NR) CR/CRh rate, n (%); 95% CI 38 (41); 30.8, 51.5 13 (24); 13.5, 37.6 DOR, median months (95% CI) 25.3 (12.0, NR) NR (8.7, NR) OS, median months (95% CI) 13.0 (9.3, 18.9) 8.9 (5.8, 14.9) NR, not reached.

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