ALBERT

Description: Introduction: In the phase 3 QuANTUM-R trial, once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefits vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); P = .02]; composite complete remission [CRc], 48% vs 27%; median duration of CRc, 12.1 vs 5.0 wk) in 367 pts with R/R FLT3-ITD AML (Cortes et al. Lancet Oncol, 2019; NCT02039726). Prior to randomization, 25% (Q) and 23% (SC) of pts had 1 prior HSCT. An OS sensitivity analysis, with censoring at the time of any subsequent HSCT during QuANTUM-R, was supportive (mOS, 5.7 vs 4.6 mo [HR, 0.79 (95% CI, 0.59-1.05)]; P = .05). Post hoc analyses of characteristics and clinical outcomes in pts who underwent subsequent HSCT in QuANTUM-R are reported. Methods: Pts aged ≥ 18 y with FLT3-ITD R/R AML receiving Q (60 mg [30-mg lead-in]) or 1 of 3 prespecified high- or low-intensity SC regimens and underwent subsequent HSCT as part of the open-label, randomized QuANTUM-R trial were analyzed. Pts receiving HSCT in the Q arm could resume maintenance Q 30-100 days after HSCT. Decisions to proceed to HSCT and resume Q after HSCT were made per investigator discretion/institutional policies. Results: Of 367 randomized pts, 85 in the Q arm underwent any subsequent HSCT (allogenic HSCT [allo-HSCT], 84 [6 with and 78 w/o additional AML therapy]; autologous HSCT, 1) and 19 in the SC arm underwent any HSCT (5 with and 14 w/o additional AML therapy]). Median age (range) was lower in pts with any HSCT (Q, 49 [19-71] y; SC, 44 [23-67] y) vs pts w/o (Q, 58 [19-81] y; SC, 59 [18-78] y). Q + SC pooled data showed a longer mOS (95% CI) in 104 pts with any HSCT vs 263 w/o (12.2 [10.0-24.1] vs 4.4 [4.1-4.9] mo; P 〈 .0001; Fig 1); 1-year OS probabilities (95% CI) were 50% (40%-60%) vs 13% (9%-18%). Among pts preselected for high-intensity therapy (Q [n = 188] + SC [n = 93]), mOS in the pooled high-intensity group was 11.9 (10.0-24.0) mo with any HSCT vs 4.6 (4.1-5.4) mo w/o. Among pts preselected for low-intensity therapy, 13/57 in the Q arm and 0/29 in the SC arm underwent any HSCT; mOS in the pooled low-intensity group was 32.4 (6.2-NA) mo with any HSCT vs 4.1 (2.7-4.6) mo w/o. In pts with CRc (last recorded response prior to allo-HSCT), mean time (range) to allo-HSCT was 13.3 (5.9-26.9) wk with Q and 12.1 (6.3-28.6) wk with SC. Q + SC pooled data showed that mOS (95% CI) was longer in pts with a CRc prior to allo-HSCT vs pts w/o CRc (20.1 [11.7-NA] vs 8.8 [7.0-11.4] mo). Survival outcomes by treatment were similar regardless of study treatment, with longer mOS in pts with any HSCT vs pts w/o (Q, 11.9 [10.2-25.1] vs 4.5 [4.1-5.4] mo; SC, 12.7 [6.1-NA] vs 4.0 [2.7-5.0] mo); respective 1-year OS probabilities (95% CI) were 50% (39%-60%) vs 13% (8%-20%) and 51% (26%-70%) vs 12% (6%-21%). In the Q arm, mOS (95% CI) was longer in pts with a best response of CRc who resumed Q after allo-HSCT (27.1 [18.2-NA] mo) vs pts not resuming Q (5.4 [4.7-11.4] mo; Fig 2). In 48 pts (62%) in the Q arm resuming Q after allo-HSCT, median time (range) from allo-HSCT to Q resumption was 65 (30-106) d. Four pts (5%) in the Q arm died 〈 30 days after allo-HSCT. As of 2/22/2018, 46 of 78 pts in the Q arm (59%) and 9 of 14 pts in the SC arm (64%) with allo-HSCT w/o additional AML therapy died, primarily due to AML disease progression (Q, 31 [40%]; SC, 7 [50%]). The frequency of treatment-emergent adverse events (TEAEs) was mostly lower in pts resuming Q after allo-HSCT than in the overall Q population (Table 1); TEAEs of interest were similar. Long-term survivor data will be presented. Conclusions: Independent of HSCT, Q improved survival vs SC in pts with FLT3-ITD R/R AML in QuANTUM-R. Q + SC pooled analyses showed longer survival in pts with HSCT vs pts w/o and in pts with CRc prior to allo-HSCT. Importantly, survival post-HSCT was similar in the Q and SC arms, indicating that pts eligible for HSCT were appropriately transplanted, and the higher HSCT rate in the Q arm was beneficial to pts. More pts treated with Q underwent HSCT, likely due to a higher rate and duration of CRc with Q vs SC and better overall fitness. In pts preselected for low-intensity SC at study entry, 13 were able to undergo HSCT after Q treatment. Resumption of Q after HSCT was associated with better survival outcomes and was tolerable. These data illustrate the value of using Q to target the FLT3-ITD mutation as a part of the overall treatment sequence in pts with FLT3-ITD R/R AML. Disclosures Ganguly: Seattle Genetics: Speakers Bureau; Janssen: Honoraria, Other: Advisory Board; Kite Pharma: Honoraria, Other: Advisory Board; Daiichi Sankyo: Research Funding. Cortes:Bristol-Myers Squibb: Consultancy, Research Funding; BiolineRx: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Merus: Consultancy, Honoraria, Research Funding. Krämer:Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Bayer: Research Funding. Levis:Amgen: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Daiichi Sankyo Inc: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Menarini: Consultancy, Honoraria; FUJIFILM: Consultancy, Research Funding. Martinelli:Daiichi Sankyo: Consultancy, Honoraria; Pfizer: Consultancy, Other: trial grant; Celgene: Consultancy, Honoraria, Other: trial grant; Janssen: Consultancy, Other: trial grant; Incyte: Consultancy, Other: trial grant; Amgen: Consultancy, Other: trial grant; Abbvie: Consultancy, Honoraria, Other: trial grant; Novartis: Consultancy, Other: trial grant; Roche: Consultancy, Other: trial grant; Ariad: Consultancy, Other: trial grant. Perl:Novartis: Honoraria, Other: Advisory board, Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of the data., Research Funding; Bayer: Research Funding; BioMed Valley Discoveries: Research Funding; FujiFilm: Research Funding; Takeda: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Astellas: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of trial data., Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding; Arog: Consultancy, Other: Non-financial support included travel costs for advisory board meetings.; AbbVie: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Actinium Pharmaceuticals: Consultancy, Honoraria, Other: Clinical Advisory Board member, Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Non-financial support included travel costs for advisory board meetings.; Jazz: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; NewLink Genetics: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.. Russell:Astellas: Consultancy, Honoraria, Speakers Bureau; Pfizer Inc: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau; DSI: Consultancy, Honoraria, Speakers Bureau. Arunachalam:Daiichi Sankyo: Employment. Gammon:Daiichi Sankyo: Consultancy. Lesegretain:Daiichi-Sankyo Inc.: Employment, Equity Ownership. Mires:Daiichi Sankyo: Employment. Namuyinga:Daiichi Sankyo: Employment. Zhang:Daiichi Sankyo: Employment. Khaled:Omeros: Consultancy; Daiichi Sankyo: Other: Travel support; Alexion: Consultancy, Speakers Bureau.

Description: Background Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations occur in 10%-15% of pediatric/adolescent patients with AML and are associated with treatment resistance, risk of relapse, and poor survival. Nearly 50% of children with newly diagnosed FLT3-ITD AML fail treatment or relapse as their first event (Levis, et al, Intl J Hematol 2005; Gilliland, Blood 2002). Therefore, targeting FLT3-ITD may improve clinical responses or prevent relapse in younger patients with FLT3-ITD mutations. No FLT3 inhibitors are approved for use in children. Q is an oral, highly potent and selective, type II FLT3 inhibitor. In the phase 3 QuANTUM-R trial, Q monotherapy prolonged overall survival vs salvage chemotherapy in adult patients with R/R FLT3-ITD AML (Cortes, et al, Lancet Oncol 2019). In another study, Q combined with chemotherapy in pediatric patients (age ≤ 21 years) with R/R AML or acute lymphoblastic leukemia, regardless of FLT3-ITD status, resulted in a marked reduction in bone marrow blasts for patients with FLT3-ITD vs other patients (Cooper, et al, Clin Cancer Res 2016). Thus, there is a strong rationale to investigate Q for treatment of R/R FLT3-ITD AML in pediatric/adolescent patients. Study Design and Methods This open-label, multicenter, single-arm, phase 1/2 study (NCT03793478) consists of dose-escalation and -expansion phases. Patients will be stratified into 2 age groups: 1 to 〈 12 months (younger age group) and 1 to ≤ 21 years (older age group). Key inclusion criteria are diagnosis of FLT3-ITD AML, first relapse or refractory to first-line high-dose chemotherapy with adequate organ function. Patients who received prior therapy with other FLT3 inhibitors or prior stem cell transplant (SCT) are eligible. Key exclusion criteria include acute promyelocytic leukemia or juvenile myelomonocytic leukemia, significant cardiovascular disease (including QTc 〉 450 ms), active systemic infections, liver disease, or HIV infection. Phases 1 and 2 include ≤ 2 reinduction cycles, optional consolidation therapy, and continuation therapy for those having a partial response (PR) or remission. Reinduction therapy will consist of fludarabine and cytarabine (FLA; 30 mg/m2/day and 2000 mg/m2/day, respectively) followed by Q in 28-day cycles. Patients will be treated with intrathecal (IT) triple chemotherapy prophylaxis before reinduction cycles 1 and 2 and after cycle 2. Additional IT triple chemotherapy prophylaxis may be given at investigator discretion for patients with CNS2 disease. Patients achieving at least a PR after reinduction may receive optional consolidation chemotherapy as a bridge to allogeneic hematopoietic SCT (HSCT). Optional consolidation regimens are high-intensity chemotherapy (cytarabine 500 mg/m2/day + etoposide 100 mg/m2/day) followed by Q, or low-intensity consolidation with either Q monotherapy or cytarabine (75 mg/m2/day). Patients who achieve at least a PR after reinduction or continue to be in remission after HSCT may receive continuation therapy with Q monotherapy (for up to twelve 28-day cycles). In phase 1, the starting dose of Q for the reinduction cycle for patients 1 to ≤ 21 years will be 40 mg/m2 once daily with body surface area (BSA) 〈 1.5 m2 or 60 mg once daily for patients with BSA ≥ 1.5 m2. The starting dose of Q for younger patients in phase 1 will be determined from the recommended phase 2 dose (RP2D) from the older age group and pharmacokinetic (PK) modeling. Up to 9 patients per dose level will be enrolled in the older age group, and younger patients will be enrolled using a rolling 6 design. Patients in phase 2 will receive the RP2D for their respective age group. The planned sample size is 41-65 patients to meet the target of 41 response-evaluable patients at the RP2D. QTc based dose modifications will be instituted for Q. The primary endpoints are safety, composite complete remission rate (CRc; defined as complete remission + complete remission with incomplete recovery), and PK parameters. Secondary endpoints include duration of responses, relapse rates, overall survival, and event-free survival at 1, 2, and 3 years, number of patients proceeding to HSCT, pharmacodynamics, gene mutations in bone marrow blasts, minimal residual disease, and FLT3 allelic ratio. This study is recruiting and being conducted in collaboration with the Children's Oncology Group in North America and the Innovative Therapies for Children with Cancer Consortium in Europe. Disclosures Zwaan: Servier: Consultancy; Pfizer: Research Funding; BMS: Research Funding; Janssen: Consultancy; Roche: Consultancy; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Jazz Pharmaceuticals: Other: Travel support; Incyte: Consultancy; Novartis: Consultancy. Mires:Daiichi Sankyo: Employment. Vigliotti:Daiichi Sankyo, Inc.: Employment. Xie:Daiichi Sankyo, Inc.: Employment. Downs:Daiichi Sankyo, Inc.: Employment. DeCillis:Pyramid: Consultancy; Codiak: Consultancy; Eleven: Consultancy; Arvinas: Consultancy; Exelixis: Consultancy; Novartis: Consultancy; Genocea: Consultancy; Daiichi Sankyo, Inc.: Consultancy; CytomX: Consultancy.

Description: Background: Quizartinib, a once-daily, oral, highly potent and selective FLT3 inhibitor, demonstrated a significant improvement in survival vs SC in FLT3-ITD-positive R/R AML in the global, randomized, phase 3 QuANTUM-R study (Cortes et al. Lancet Oncol, 2019; NCT02039726). Patients with R/R FLT3-ITD-positive AML were randomized 2:1 to receive single agent quizartinib or investigator's choice of pre-selected SC. We investigated the effects of baseline co-mutations and FLT3-ITD VAF on overall survival (OS) and response (composite complete remission [CRc]) to quizartinib and SC in QuANTUM-R. Methods: We analyzed 37 recurrently mutated genes in AML in baseline bone marrow samples from 304 patients (82.8% of ITT population [N = 367; quizartinib, n = 245; SC, n = 122]) with R/R FLT3-ITD-positive AML using next-generation sequencing and a customized Archer® Core Myeloid panel. Positive mutation status was defined as ≥ 1 mutation detected in the gene region using a VAF cutoff of 2.7%. FLT3-ITD VAF was measured separately by the Navigate BioPharma FLT3 Mutation Assay (polymerase chain reaction-based, VAF cutoff of 3%). Low and high FLT3-ITD VAF were defined as ≤25% and 〉25%, respectively. Results: In addition to FLT3-ITD, 5 key co-mutations were detected: DNMT3Amut (n = 182/304 [59.9%]), NPM1mut (n = 168/304 [55.3%]), TET2mut (n = 98/304 [32.2%]), IDH1/2mut (n = 49/304 [16.1%]) and CEBPAmut (n = 46/304 [15.1%]). Median OS was numerically longer with quizartinib vs SC in patients with DNMT3Amut, TET2mut, IDH1/2mut and NPM1mut, but not CEBPAmut (Table). CRc rates were numerically higher with quizartinib vs SC for each of the 5 key baseline co-mutations. For single gene mutations, the longest median OS was seen in patients with CEBPAmut treated with quizartinib or SC (37 and 37.6 weeks, respectively). As the majority of NPM1mut patients were also DNMT3Amut (138/168, 82%), we examined various permutations of these two mutations. Patients with NPM1wt/DNMT3Amut had significantly longer median OS with quizartinib vs SC (39.3 vs 19.6 weeks, respectively; HR, 0.239; P = 0.003 [Table]) while NPM1mut/DNMT3Amut patients had lower and similar median OS between the 2 arms (23.6 vs 23.4 weeks, respectively). Quizartinib treatment showed significantly longer median OS vs SC in patients with high FLT3-ITD VAF (23.9 vs 17 weeks respectively; HR, 0.689, P = 0.0148), while the median OS in patients with low FLT3-ITD VAF was similar (34.1 vs 26.6 weeks, respectively; HR, 0.857, P = 0.535). Conclusions: This is the first evaluation of the effect of baseline co-mutations on clinical outcomes in a large trial of R/R AML patients with FLT3-ITD mutations treated with quizartinib. Key co-mutations identified in this analysis were found to potentially impact treatment response and OS with quizartinib, relative to SC. Despite relatively low CRc rates in patients with IDH1/2mut, this group-as well as those with NPM1wt-derived the greatest OS benefit from quizartinib compared with SC on QuANTUM-R. CEBPA mutations were associated with high CRc rates and relatively long median OS, regardless of treatment arm. Patients with NPM1mut had a higher CRc rate with quizartinib vs SC, but this did not translate into longer survival on either arm compared with NPM1wt. A high allelic burden of FLT3-ITD at the time of salvage therapy was associated with relatively poorer median OS; quizartinib significantly improved survival of patients with high FLT3-ITD VAF relative to SC. Although these results require confirmation in an independent dataset, the modulatory effects of baseline co-mutations on treatment response and OS with quizartinib appear to differ from other FLT3 inhibitors. Our results indicate that a subset of R/R AML patients may particularly derive clinical benefit from quizartinib. Table Disclosures Perl: Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding; Arog: Consultancy, Other: Non-financial support included travel costs for advisory board meetings.; AbbVie: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Actinium Pharmaceuticals: Consultancy, Honoraria, Other: Clinical Advisory Board member, Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Non-financial support included travel costs for advisory board meetings.; Jazz: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; NewLink Genetics: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Takeda: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Bayer: Research Funding; BioMed Valley Discoveries: Research Funding; FujiFilm: Research Funding; Novartis: Honoraria, Other: Advisory board, Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of the data., Research Funding; Astellas: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of trial data., Research Funding. Cortes:Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding. Ganguly:Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board; Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Research Funding. Khaled:Omeros: Consultancy; Alexion: Consultancy, Speakers Bureau; Daiichi Sankyo: Other: Travel support. Krämer:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; BMS: Research Funding. Martinelli:Novartis: Consultancy, Other: trial grant; Roche: Consultancy, Other: trial grant; Janssen: Consultancy, Other: trial grant; Incyte: Consultancy, Other: trial grant; Pfizer: Consultancy, Other: trial grant; Amgen: Consultancy, Other: trial grant; Celgene: Consultancy, Honoraria, Other: trial grant; Ariad: Consultancy, Other: trial grant; Abbvie: Consultancy, Honoraria, Other: trial grant; Daiichi Sankyo: Consultancy, Honoraria. Russell:Pfizer Inc: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau; DSI: Consultancy, Honoraria, Speakers Bureau. Chang:Daiichi Sankyo: Employment. Mires:Daiichi Sankyo: Employment. Kato:Daiichi Sankyo, Inc.: Employment; Celgene: Employment, Equity Ownership. Zhang:Daiichi Sankyo: Employment. Korkhov:Precision for Medicine, Inc.: Employment; Daiichi Sankyo: Consultancy. Wang:Precision for Medicine, Inc.: Employment; Daiichi Sankyo: Consultancy. Günnel:Precision for Medicine, Inc.: Employment; Daiichi Sankyo: Consultancy. Sumi:Daiichi Sankyo, Inc.: Employment. Isoyama:Daiichi Sankyo Co, Ltd: Employment. Lesegretain:Daiichi-Sankyo Inc.: Employment, Equity Ownership. Berisha:Daiichi Sankyo: Employment. Dos Santos:Daiichi Sankyo: Employment. Levis:Agios: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; FUJIFILM: Consultancy, Research Funding; Menarini: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; Daiichi Sankyo Inc: Consultancy, Honoraria.

Description: Introduction: Patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) with FLT3-ITD mutations have a dismal prognosis and limited treatment options. Given the aggressiveness of FLT3-ITD AML, therapies that produce rapid and sustained disease control are needed. Quizartinib (Q), a once-daily, oral, highly potent and selective FLT3 inhibitor, demonstrated a clinically meaningful overall survival (OS) benefit in pts with R/R FLT3-ITD AML vs salvage chemotherapy (SC; 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); P = .02]) in the phase 3 QuANTUM-R trial (NCT02039726; Cortes et al. Lancet Oncol, 2019). In this post hoc analysis, we characterize clinical outcomes in pts who achieved a composite complete remission (CRc) in QuANTUM-R, including pts with CR with incomplete hematologic recovery (CRi) and transfusion independence. Methods: Pts aged ≥ 18 years with FLT3-ITD AML R/R after standard AML therapy, with or without hematopoietic stem cell transplant (HSCT), were randomized 2:1 to Q (60 mg [30-mg lead-in]) or 1 of 3 prespecified SC regimens. Pts receiving HSCT in the Q arm could resume Q after HSCT. Response was assessed per modified International Working Group criteria (Table 1). Transfusion dependence at baseline (BL) was defined as any platelet (PLT) or red blood cell (RBC) transfusion within 28 days of first dose. Post-BL transfusion independence was defined as no PLT or RBC transfusions for any consecutive 56-day period on treatment. Results: Of 367 randomized pts, 245 and 122 were randomized to Q and SC, respectively. Median duration of treatment was 97 days with Q (including post-HSCT resumption) and ranged from 5 to 10 days with SC depending on the regimen. Median follow-up was 23.5 mo. In the intent-to-treat population, CRc was consistent across prespecified subgroups (eg, sex, response to prior therapy, FLT3-ITD variant allele frequency). Median time to CRc was 1.1 mo with Q and 0.9 mo with SC; median duration of CRc was 2.8 mo with Q and 1.2 mo with SC (Table 2). Most responses in both arms were CRi, achieved in 99 pts (40%) in the Q arm and 32 pts (26%) in the SC arm. Peripheral blood counts in pts who achieved CRi are shown in Table 3. Of pts with CRi, 45 (Q) and 13 (SC) underwent HSCT. Outcomes with HSCT included engraftment failure in 11% (Q), rejection in 2% (Q), relapse in 33% (Q) and 46% (SC), and successful transplant in 47% (Q) and 46% (SC) and were unknown in 7% (Q) and 8% (SC). Of the 205 pts in the Q arm who were transfusion dependent at BL, 46 (22%) became transfusion independent post-BL (29 with HSCT; 17 without). Mean (SD) duration of post-BL transfusion independence was 255 (216.6) days. By response, 24 of 91 pts (26%) with CRi, 7 of 48 (15%) with a partial response (PR), and 4 of 47 (9%) with no response (NR) became transfusion independent post-BL; respective mean (SD) durations were 297.6 (268.3), 84.6 (21.7), and 211.3 (111.9) days. Of the 36 pts in the Q arm who were transfusion independent at BL, 20 (55.6%) maintained transfusion independence post-BL (12 with HSCT; 8 without; mean [SD] duration, 208 [203.1] days). Transfusion independence could not be assessed in the SC arm. Transfusion data was not collected after the end of treatment, and most pts in the SC arm were treated for 〈 56 days. In the Q arm, median OS (95% CI) was longer in pts with CRi (7.5 [5.4-9.9] mo) vs pts with PR (6.1 [5.1-7.2] mo) or NR (4.1 [3.3-5.9] mo) (Figure 1); respective medians in the SC arm were 8.8 (6.3-20.8), 7.8 (5.4-28.2), and 3.8 (2.7-4.7) mo. In the 34 pts in the Q arm with a last response of CRi prior to allogeneic HSCT, median OS (95% CI) was 25.1 (9.9-NA) mo; in the SC arm (n = 9), median OS (95% CI) was 20.1 (4.3-NA) mo. In the Q arm, median OS (95% CI) was longer in pts with CRi who became transfusion independent post-BL vs pts who did not (27.1 [10.4-NA] vs 5.3 [4.6-6.4] mo); similarly, median OS (95% CI) was longer in pts who maintained transfusion independence vs pts who did not (25.1 [11.4-NA] vs 9.6 [4.6-NA] mo). Conclusions: Q induced rapid, durable, and consistent tumor control in pts with FLT3-ITD R/R AML irrespective of prior therapy, including HSCT. A high proportion of pts with CRi became eligible for HSCT, the only potential curative treatment option. Moreover, a high proportion achieved durable transfusion independence regardless of HSCT, which is also associated with clinical benefit. These data highlight the clinical benefit of achieving CRi with Q in pts with FLT3-ITD R/R AML, a population with a high unmet need. Disclosures Levis: Novartis: Consultancy, Research Funding; Daiichi Sankyo Inc: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Astellas: Consultancy, Research Funding; Amgen: Consultancy, Honoraria; FUJIFILM: Consultancy, Research Funding; Menarini: Consultancy, Honoraria. Ganguly:Daiichi Sankyo: Research Funding; Seattle Genetics: Speakers Bureau; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board. Khaled:Alexion: Consultancy, Speakers Bureau; Daiichi Sankyo: Other: Travel support; Omeros: Consultancy. Krämer:BMS: Research Funding; Bayer: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees. Martinelli:Novartis: Consultancy, Other: trial grant; Pfizer: Consultancy, Other: trial grant; Roche: Consultancy, Other: trial grant; Incyte: Consultancy, Other: trial grant; Ariad: Consultancy, Other: trial grant; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: trial grant; Amgen: Consultancy, Other: trial grant; Abbvie: Consultancy, Honoraria, Other: trial grant; Janssen: Consultancy, Other: trial grant. Perl:BioMed Valley Discoveries: Research Funding; FujiFilm: Research Funding; Novartis: Honoraria, Other: Advisory board, Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of the data., Research Funding; Takeda: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Bayer: Research Funding; NewLink Genetics: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Actinium Pharmaceuticals: Consultancy, Honoraria, Other: Clinical Advisory Board member, Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Non-financial support included travel costs for advisory board meetings.; Jazz: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.; Astellas: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings as well as a medical writing company that assisted with manuscript preparation/submission and slide deck assembly for academic meeting presentations of trial data., Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Other, Research Funding; Arog: Consultancy, Other: Non-financial support included travel costs for advisory board meetings.; AbbVie: Consultancy, Honoraria, Other: Non-financial support included travel costs for advisory board meetings.. Russell:Astellas: Consultancy, Honoraria, Speakers Bureau; DSI: Consultancy, Honoraria, Speakers Bureau; Pfizer Inc: Consultancy, Honoraria, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau. Choi:Daiichi Sankyo: Employment. Lesegretain:Daiichi-Sankyo Inc.: Employment, Equity Ownership. Mendell:Daiichi Sankyo, Inc.: Employment. Mires:Daiichi Sankyo: Employment. Zhang:Daiichi Sankyo: Employment. Cortes:Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Sun Pharma: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding.