Context: FLAG-IDA induction results in complete remission in approximately 85% of newly diagnosed patients with acute myeloid leukemia (ND-AML), however 30-40% experience relapse. Combining the BCL-2 inhibitor venetoclax (VEN) with chemotherapy improves efficacy, inferring FLAG-IDA+VEN may improve outcomes in ND-AML. Objectives: The primary P2 objective was determination of the overall activity of FLAG-IDA+VEN. Key secondary objectives include overall response rate (ORR: CR+CRi+CRh+MLFS+PR), CRc (CR+ CRh+CRi), overall survival (OS), event-free survival (EFS), and duration of response (DOR). Design: A Phase 1b/2 study evaluating FLAG-IDA+VEN in ND and relapsed/refractory (R/R) AML patients ≥ 18 years of age. Phase 1b results were previously reported (DiNardo, JCO 2021). The Phase 2 (P2) portion enrolled patients into two cohorts: ND-AML (n=38), and R/R-AML (n=39). ND-AML outcomes are reported herein. Results: Thirty-eight patients with ND-AML (sAML: n=7, therapy-related AML: n=5) enrolled. Median age was 44 years (range 20-65). ELN risk was favorable, intermediate, and adverse in 18%, 37%, and 45% of patients. Three patients were too early for response evaluation. The ORR was 94% (CR: n=24 [69%], CRh: n=5 [14%], CRi: n=1 [3%], MLFS: n=3 [9%]) and corresponding CRc rate was 86% (n=30). 93% of CRc patients attained MRD-negative status. Patients received a median of 2 (range: 1-6) cycles. 57% (n=20) transitioned to allogeneic stem-cell transplant (HSCT). Median DOR was 18.4 (95% CI: 13.1-21.1) months. Median cycle length for cycles 1 and 2 were 31 and 41 days. No 30 or 60-day mortality occurred. Common adverse events included febrile neutropenia (34%), pneumonia (28%), cellulitis (16%), and bacteremia (16%). Eight patients relapsed (ELN intermediate: N=3, ELN adverse: N=5) including 100% of patients with baseline TP53 mutations (N= 4); and there have been 4 deaths, all in relapsed patients. Five relapses and three of four deaths occurred post-HSCT. After a median study follow up of 15 months, median EFS and OS were NR, with 1-year EFS and OS rates of 76% and 96%, respectively. Conclusions: FLAG-IDA+VEN induction and consolidation results in high MRD-negative composite CR rates in ND-AML with an expected safety profile. Durable responses were observed at 12-months. Long-term follow up is ongoing to confirm these results. FLAG-IDA induction results in complete remission in approximately 85% of newly diagnosed patients with acute myeloid leukemia (ND-AML), however 30-40% experience relapse. Combining the BCL-2 inhibitor venetoclax (VEN) with chemotherapy improves efficacy, inferring FLAG-IDA+VEN may improve outcomes in ND-AML. The primary P2 objective was determination of the overall activity of FLAG-IDA+VEN. Key secondary objectives include overall response rate (ORR: CR+CRi+CRh+MLFS+PR), CRc (CR+ CRh+CRi), overall survival (OS), event-free survival (EFS), and duration of response (DOR). A Phase 1b/2 study evaluating FLAG-IDA+VEN in ND and relapsed/refractory (R/R) AML patients ≥ 18 years of age. Phase 1b results were previously reported (DiNardo, JCO 2021). The Phase 2 (P2) portion enrolled patients into two cohorts: ND-AML (n=38), and R/R-AML (n=39). ND-AML outcomes are reported herein. Thirty-eight patients with ND-AML (sAML: n=7, therapy-related AML: n=5) enrolled. Median age was 44 years (range 20-65). ELN risk was favorable, intermediate, and adverse in 18%, 37%, and 45% of patients. Three patients were too early for response evaluation. The ORR was 94% (CR: n=24 [69%], CRh: n=5 [14%], CRi: n=1 [3%], MLFS: n=3 [9%]) and corresponding CRc rate was 86% (n=30). 93% of CRc patients attained MRD-negative status. Patients received a median of 2 (range: 1-6) cycles. 57% (n=20) transitioned to allogeneic stem-cell transplant (HSCT). Median DOR was 18.4 (95% CI: 13.1-21.1) months. Median cycle length for cycles 1 and 2 were 31 and 41 days. No 30 or 60-day mortality occurred. Common adverse events included febrile neutropenia (34%), pneumonia (28%), cellulitis (16%), and bacteremia (16%). Eight patients relapsed (ELN intermediate: N=3, ELN adverse: N=5) including 100% of patients with baseline TP53 mutations (N= 4); and there have been 4 deaths, all in relapsed patients. Five relapses and three of four deaths occurred post-HSCT. After a median study follow up of 15 months, median EFS and OS were NR, with 1-year EFS and OS rates of 76% and 96%, respectively. FLAG-IDA+VEN induction and consolidation results in high MRD-negative composite CR rates in ND-AML with an expected safety profile. Durable responses were observed at 12-months. Long-term follow up is ongoing to confirm these results.