Background: Patients with acute myeloid leukemia (AML) in remission are at high risk of relapse, warranting remission-prolonging therapy. Gilteritinib is the first FMS-like tyrosine kinase 3 (FLT3) inhibitor approved as monotherapy in FLT3-mutated relapsed/refractory AML. The aim of the study was to compare relapse-free survival (RFS) in patients with FLT3/internal tandem duplication AML in first complete remission who received gilteritinib or placebo.

Method: In this phase 2, double-blind trial, patients were randomized 2:1 to gilteritinib (120 mg) or placebo once daily for up to 2 years, beginning after completion of induction/consolidation (I/C) therapy. RFS, defined as time from randomization date until the date of documented relapse or death from any cause was assessed via independent review committee adjudication (primary efficacy endpoint). Overall survival (OS) was defined as the time from date of randomization until date of death from any cause. Survival and treatment-emergent adverse events (TEAEs) were assessed 30 days after treatment discontinuation, and every 3 months thereafter. Due to a slow accrual rate, this trial (NCT02927262) was changed from a planned phase 3 to phase 2 based on the reduction in sample size.

Results: 124 patients were screened and 98 were randomized (gilteritinib 63, placebo 35) and are included in the full analysis set (FAS), of whom 32 (gilteritinib 20, placebo 12) completed 2 years of treatment. The safety analysis set (SAF) comprised 97 patients (gilteritinib 62, placebo 35) who had received ≥1 dose of study drug. In the FAS, relapse occurred in 31/63 (49.2%) gilteritinib- and 20/35 (57.1%) placebo-treated patients; 3/63 (4.8%) gilteritinib-treated patients died without relapse. RFS was not significantly improved with gilteritinib vs placebo (hazard ratio [HR] 0.738, 95% confidence interval [CI] 0.407-1.336; 1-sided stratified log-rank p-value 0.163). Median RFS was 24.02 months for gilteritinib and 15.84 months for placebo. OS in the FAS was not significantly different between treatments (gilteritinib 21/63, [33.3%], placebo 11/35 [31.4%]; HR 1.130, 95% CI 0.540-2.364; 1-sided stratified log-rank p-value 0.627). Median OS was not reached in either arm. TEAEs in the SAF occurred in 58/62 (93.5%) gilteritinib- and 33/35 (94.3%) placebo-treated patients including, respectively, 51/62 (82.3%) and 20/35 (57.1%) drug-related TEAEs and 10/62 (16.1%) and 3/35 (8.6%) serious drug-related TEAEs. The most common TEAEs were increased blood creatine phosphokinase (gilteritinib 18/62 [29.0%], placebo 1/35 [2.9%]) and thrombocytopenia (gilteritinib 12/62 [19.4%], placebo 4/35 [11.4%]).

Conclusion: Gilteritinib showed improved RFS versus placebo, but the difference was not statistically significant. There were no new safety findings in the gilteritinib arm.

Citation Format: Mark D. Minden, Jacob M. Rowe, Emmanuel Gyan, Kohmei Kubo, Nahla Hasabou, David Delgado, Wensheng He, Stanley C. Gill, Jason E. Hill, Ramon Tiu. A phase 2, multicenter, randomized, double-blind trial of maintenance therapy with FLT3 inhibitor gilteritinib (ASP2215) in patients with FLT3/ITD AML (GOSSAMER study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT537.