Summary of TEAEs
| TEAE, n (%) . | Dose escalation cohort 1: venetoclax 100 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 8 . | Dose escalation cohort 2: venetoclax 200 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 9 . | Dose escalation cohort 3: venetoclax 400 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 8 . | All patients treated at RP2D (dose escalation + expansion cohorts): venetoclax 400 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) N = 107 . |
|---|---|---|---|---|
| Any TEAE | 8 (100) | 9 (100) | 8 (100) | 107 (100) |
| Any grade 3/4 TEAE | 8 (100) | 9 (100) | 8 (100) | 101 (94.4) |
| TEAE possibly related to venetoclax | 8 (100) | 8 (88.9) | 6 (75.0) | 101 (94.4) |
| TEAE possibly related to azacitidine | 8 (100) | 9 (100) | 6 (75.0) | 99 (92.5) |
| TEAE leading to dose-limiting toxicities | 0 | 0 | 0 | 0 |
| Any serious AE | 5 (62.5) | 7 (77.8) | 8 (100) | 73 (68.2) |
| Death | 6 (75.0) | 8 (88.9) | 3 (37.5) | 59 (55.1)∗ |
| TEAEs occurring in ≥20% of patients | ||||
| Constipation | 6 (75.0) | 8 (88.9) | 3 (37.5) | 57 (53.3) |
| Nausea | 3 (37.5) | 4 (44.4) | 4 (50.0) | 53 (49.5) |
| Neutropenia | 5 (62.5) | 4 (44.4) | 1 (12.5) | 52 (48.6) |
| Thrombocytopenia | 4 (50.0) | 7 (77.8) | 0 | 48 (44.9) |
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 45 (42.1) |
| Diarrhea | 5 (62.5) | 5 (55.6) | 3 (37.5) | 44 (41.1) |
| Anemia | 3 (37.5) | 2 (22.2) | 2 (25.0) | 42 (39.3) |
| Vomiting | 2 (25.0) | 3 (33.3) | 3 (37.5) | 39 (36.4) |
| Hypokalemia | 3 (37.5) | 1 (11.1) | 3 (37.5) | 28 (26.2) |
| Fatigue | 1 (12.5) | 3 (33.3) | 1 (12.5) | 23 (21.5) |
| Grade 3/4 TEAEs occurring in ≥10% of patients | ||||
| Anemia | 2 (25.0) | 2 (22.2) | 2 (25.0) | 37 (34.6) |
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 45 (42.1)† |
| Leukopenia | 1 (12.5) | 2 (22.2) | 0 | 20 (18.7) |
| Neutropenia | 5 (62.5) | 4 (44.4) | 1 (12.5) | 52 (48.6)† |
| Thrombocytopenia | 2 (25.0) | 7 (77.8) | 0 | 46 (43.0) |
| Pneumonia | 0 | 1 (11.1) | 1 (12.5) | 12 (11.2) |
| Neutrophil count decreased | 3 (37.5) | 1 (11.1) | 3 (37.5) | 16 (15.0)† |
| Platelet count decreased | 1 (12.5) | 1 (11.1) | 0 | 12 (11.2) |
| White blood cell count decreased | 1 (12.5) | 2 (22.2) | 2 (25.0) | 18 (16.8) |
| Serious AEs occurring in ≥5% of patients | ||||
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 39 (36.4) |
| Pneumonia | 0 | 1 (11.1) | 1 (12.5) | 7 (6.5) |
| Cellulitis | 0 | 1 (11.1) | 0 | 6 (5.6) |
| Diverticulitis | 0 | 1 (11.1) | 0 | 6 (5.6) |
| Sepsis | 0 | 1 (11.1) | 0 | 6 (5.6) |
| TEAE, n (%) . | Dose escalation cohort 1: venetoclax 100 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 8 . | Dose escalation cohort 2: venetoclax 200 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 9 . | Dose escalation cohort 3: venetoclax 400 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) n = 8 . | All patients treated at RP2D (dose escalation + expansion cohorts): venetoclax 400 mg (14 d/cycle) + azacitidine 75 mg/m2 (7 d/cycle) N = 107 . |
|---|---|---|---|---|
| Any TEAE | 8 (100) | 9 (100) | 8 (100) | 107 (100) |
| Any grade 3/4 TEAE | 8 (100) | 9 (100) | 8 (100) | 101 (94.4) |
| TEAE possibly related to venetoclax | 8 (100) | 8 (88.9) | 6 (75.0) | 101 (94.4) |
| TEAE possibly related to azacitidine | 8 (100) | 9 (100) | 6 (75.0) | 99 (92.5) |
| TEAE leading to dose-limiting toxicities | 0 | 0 | 0 | 0 |
| Any serious AE | 5 (62.5) | 7 (77.8) | 8 (100) | 73 (68.2) |
| Death | 6 (75.0) | 8 (88.9) | 3 (37.5) | 59 (55.1)∗ |
| TEAEs occurring in ≥20% of patients | ||||
| Constipation | 6 (75.0) | 8 (88.9) | 3 (37.5) | 57 (53.3) |
| Nausea | 3 (37.5) | 4 (44.4) | 4 (50.0) | 53 (49.5) |
| Neutropenia | 5 (62.5) | 4 (44.4) | 1 (12.5) | 52 (48.6) |
| Thrombocytopenia | 4 (50.0) | 7 (77.8) | 0 | 48 (44.9) |
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 45 (42.1) |
| Diarrhea | 5 (62.5) | 5 (55.6) | 3 (37.5) | 44 (41.1) |
| Anemia | 3 (37.5) | 2 (22.2) | 2 (25.0) | 42 (39.3) |
| Vomiting | 2 (25.0) | 3 (33.3) | 3 (37.5) | 39 (36.4) |
| Hypokalemia | 3 (37.5) | 1 (11.1) | 3 (37.5) | 28 (26.2) |
| Fatigue | 1 (12.5) | 3 (33.3) | 1 (12.5) | 23 (21.5) |
| Grade 3/4 TEAEs occurring in ≥10% of patients | ||||
| Anemia | 2 (25.0) | 2 (22.2) | 2 (25.0) | 37 (34.6) |
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 45 (42.1)† |
| Leukopenia | 1 (12.5) | 2 (22.2) | 0 | 20 (18.7) |
| Neutropenia | 5 (62.5) | 4 (44.4) | 1 (12.5) | 52 (48.6)† |
| Thrombocytopenia | 2 (25.0) | 7 (77.8) | 0 | 46 (43.0) |
| Pneumonia | 0 | 1 (11.1) | 1 (12.5) | 12 (11.2) |
| Neutrophil count decreased | 3 (37.5) | 1 (11.1) | 3 (37.5) | 16 (15.0)† |
| Platelet count decreased | 1 (12.5) | 1 (11.1) | 0 | 12 (11.2) |
| White blood cell count decreased | 1 (12.5) | 2 (22.2) | 2 (25.0) | 18 (16.8) |
| Serious AEs occurring in ≥5% of patients | ||||
| Febrile neutropenia | 2 (25.0) | 3 (33.3) | 5 (62.5) | 39 (36.4) |
| Pneumonia | 0 | 1 (11.1) | 1 (12.5) | 7 (6.5) |
| Cellulitis | 0 | 1 (11.1) | 0 | 6 (5.6) |
| Diverticulitis | 0 | 1 (11.1) | 0 | 6 (5.6) |
| Sepsis | 0 | 1 (11.1) | 0 | 6 (5.6) |
Seven patients in survival follow-up experienced AEs resulting in death, including 1 patient with neutropenic sepsis leading to death that was possibly related to venetoclax, and 2 patients with neutropenic sepsis and death (1 patient each) that were possibly related to azacitidine treatment.
Eighty-three of 107 of patients (77.6%) at the RP2D experienced a grade 3/4 neutropenic event including any of the following: neutropenia, neutrophil count decreased, febrile neutropenia, and neutropenic sepsis.