Overview of safety
| Safety characteristic . | Cohorts 1a and 1b (N = 125) . |
|---|---|
| Any TEAE | 125 (100) |
| Most common TEAEs (≥10% patients) of any grade | |
| Thrombocytopenia | 108 (86) |
| Diarrhea | 74 (59) |
| Anemia | 54 (43) |
| Nausea | 39 (31) |
| Fatigue | 37 (30) |
| Neutropenia | 33 (26) |
| COVID-19 infection | 25 (20) |
| Abdominal pain | 22 (18) |
| Arthralgia | 20 (16) |
| Contusion | 20 (16) |
| Dizziness | 19 (15) |
| Headache | 19 (15) |
| Hyperuricemia | 19 (15) |
| Alanine aminotransferase increased | 17 (14) |
| White blood cell count decreased | 17 (14) |
| Constipation | 15 (12) |
| Edema peripheral | 15 (12) |
| Pyrexia | 15 (12) |
| Decreased appetite | 14 (11) |
| Urinary tract infection | 14 (11) |
| Vomiting | 14 (11) |
| Aspartate aminotransferase increased | 13 (10) |
| Blood bilirubin increased | 13 (10) |
| Dyspnea | 13 (10) |
| Upper respiratory tract infection | 13 (10) |
| Any grade ≥3 AE | 101 (81) |
| Most common grade ≥3 TEAEs (≥10% patients) | |
| Thrombocytopenia | 66 (53) |
| Grade 3 | 64 (51) |
| Grade 4 | 18 (14) |
| Anemia (all grade 3) | 43 (34) |
| Neutropenia | 24 (19) |
| Grade 3 | 23 (18) |
| Grade 4 | 9 (7) |
| Serious TEAEs | 48 (38) |
| TEAEs leading to navitoclax discontinuation∗ | 33 (26) |
| Key TEAEs leading to navitoclax discontinuation† | |
| Thrombocytopenia | 9 (7) |
| Diarrhea | 4 (3) |
| Neuroendocrine carcinoma of the skin | 2 (2) |
| TEAEs leading to ruxolitinib discontinuation∗ | 18 (14) |
| Key TEAEs leading to ruxolitinib discontinuation† | |
| Thrombocytopenia | 4 (3) |
| TEAE leading to navitoclax interruption | 84 (67) |
| TEAE leading to ruxolitinib interruption | 57 (46) |
| TEAE leading to navitoclax reduction | 90 (72) |
| TEAE leading to ruxolitinib reduction | 77 (62) |
| TEAE leading to death‡ | 11 (9) |
| All deaths | 29 (23) |
| Deaths occurring ≤30 d after last dose of navitoclax | 11 (9) |
| Deaths occurring >30 d after last dose of navitoclax | 18 (14) |
| Safety characteristic . | Cohorts 1a and 1b (N = 125) . |
|---|---|
| Any TEAE | 125 (100) |
| Most common TEAEs (≥10% patients) of any grade | |
| Thrombocytopenia | 108 (86) |
| Diarrhea | 74 (59) |
| Anemia | 54 (43) |
| Nausea | 39 (31) |
| Fatigue | 37 (30) |
| Neutropenia | 33 (26) |
| COVID-19 infection | 25 (20) |
| Abdominal pain | 22 (18) |
| Arthralgia | 20 (16) |
| Contusion | 20 (16) |
| Dizziness | 19 (15) |
| Headache | 19 (15) |
| Hyperuricemia | 19 (15) |
| Alanine aminotransferase increased | 17 (14) |
| White blood cell count decreased | 17 (14) |
| Constipation | 15 (12) |
| Edema peripheral | 15 (12) |
| Pyrexia | 15 (12) |
| Decreased appetite | 14 (11) |
| Urinary tract infection | 14 (11) |
| Vomiting | 14 (11) |
| Aspartate aminotransferase increased | 13 (10) |
| Blood bilirubin increased | 13 (10) |
| Dyspnea | 13 (10) |
| Upper respiratory tract infection | 13 (10) |
| Any grade ≥3 AE | 101 (81) |
| Most common grade ≥3 TEAEs (≥10% patients) | |
| Thrombocytopenia | 66 (53) |
| Grade 3 | 64 (51) |
| Grade 4 | 18 (14) |
| Anemia (all grade 3) | 43 (34) |
| Neutropenia | 24 (19) |
| Grade 3 | 23 (18) |
| Grade 4 | 9 (7) |
| Serious TEAEs | 48 (38) |
| TEAEs leading to navitoclax discontinuation∗ | 33 (26) |
| Key TEAEs leading to navitoclax discontinuation† | |
| Thrombocytopenia | 9 (7) |
| Diarrhea | 4 (3) |
| Neuroendocrine carcinoma of the skin | 2 (2) |
| TEAEs leading to ruxolitinib discontinuation∗ | 18 (14) |
| Key TEAEs leading to ruxolitinib discontinuation† | |
| Thrombocytopenia | 4 (3) |
| TEAE leading to navitoclax interruption | 84 (67) |
| TEAE leading to ruxolitinib interruption | 57 (46) |
| TEAE leading to navitoclax reduction | 90 (72) |
| TEAE leading to ruxolitinib reduction | 77 (62) |
| TEAE leading to death‡ | 11 (9) |
| All deaths | 29 (23) |
| Deaths occurring ≤30 d after last dose of navitoclax | 11 (9) |
| Deaths occurring >30 d after last dose of navitoclax | 18 (14) |
All data are n (%).
Patients that discontinued the study drug could remain on the study for poststudy treatment follow-up and survival follow-up. Safety assessments were conducted for up to 30 days after study drug discontinuation.
TEAEs reported as the primary reason for treatment discontinuation (full details in supplemental Figure 1).
Multiple organ dysfunction (n = 4), COVID-19 (n = 2), pneumonia (n = 2), cardiac arrest (n = 1), infection (n = 1), septic shock (n = 1), and fall (n = 1); patients may have experienced >1 TEAE contributing to death.