Table 5 Venetoclax and immunotherapy combinations for acute myeloid leukemia.
Drug class combined with VEN | Drug combination | NCT ID | Phase | N | Status | Patient Population | Regimen |
|---|---|---|---|---|---|---|---|
Checkpoint -inhibitors | pembrolizumab (anti-PD1) + AZA + VEN [105] | NCT04284787 [105] | II | 76 | Completed | N/D | - SC AZA once daily on D1–D7 - oral VEN once daily on D1–D28 - IV pembrolizumab on D8 of cycle 1, every 3 weeks on cycle 1–6 - induction/consolidation of total six cycles - maintenance up to 24 cycles |
pembrolizumab (anti-PD1) + DEC + VEN | NCT03969446 | I | 54 | Recruiting | R/R | - unfit for intensive chemotherapy - 8 cycles of 42 days - IV pembrolizumab on D1 and D22 of every cycle - IV DEC on D1–D10 - oral VEN on D1–D14 | |
nivolumab (anti-PD1) + DEC + VEN | NCT04277442 | I | 13 | Not Recruiting | N/D | -TP53m AML - 3 cycles followed by maintenance without DEC - IV nivolumab on D1 and D15 (except cycle when with only D15) - SC or IV DEC on D1–D10 - oral VEN on D1–D21 | |
avelumab (anti-PD-L1) + AZA + VEN | NCT03390296 [106] | I/II | 50 | Completed | R/R | - IV avelumab on D1 and D14 - SC or IV AZA on D1–D7 or D1–D5 + D8–D9 - oral VEN on D1–D21 | |
magrolimumab (anti-CD47) + AZA + VEN | NCT05079230 (ENHANCE-3) | III | 378 | Completed | N/D | - unfit for intensive chemotherapy - IV magrolimumab 1 mg/kg on D1 and D4, 15 mg/kg on D8, 30 mg/kg on D11, D15 then weekly for 5 weeks and every 2 weeks thereafter - SC or IV AZA on D1–D7 - oral VEN on D1–D28 | |
NCT04435691 | II | 110 | Not Recruiting | N/D R/R | - unfit for intensive chemotherapy - 12 cycles - IV magrolimumab on D1, D4, D8, D11, D15, and D22 of cycle 1, D 1, D8, D15, and 22 of cycle 2, and D1 and D15 of cycle 3 and subsequent cycles - SC or IV AZA on D1–D7 - oral VEN on D1–D28 | ||
SL-172154 (anti-CD47) + AZA + VEN | NCT05275439 | I | 160 | Recruiting | R/R | - adverse risk AML - safety assessment | |
AK117 (anti-CD47) + AZA + VEN | NCT06387420 | I/II | 180 | Not Recruiting | R/R | - adverse risk AML - safety assessment | |
6MW3211 (anti-CD47/anti-PD-L1) + AZA + VEN | NCT05448599 | I/II | 120 | Recruiting | R/R | - fit AML patients (< 75 years) - 6MW322 once every second week - SC AZA on D1–D7 - oral VEN on D1–D28 | |
sabalolimab - MBG452 (anti-TIM3) + AZA + VEN | NCT04150029 (STIMULUS- AML1) | II | 90 | Not Recruiting | N/D | - unfit for intensive chemotherapy - 12 cycles | |
LYT-200 (anti-galectin-9) + AZA/DEC + VEN | NCT05829226 | I | 90 | Recruiting | R/R | - both fit and unfit patients eligible - IV LYT-200 once a week | |
Monoclonal antibodies | gemtuzumab ozogamicin (anti-CD33) + VEN | NCT04070768 | I | 18 | Not Recruiting | R/R | - safety assessment |
gemtuzumab ozogamicin (anti-CD33) + AZA + VEN | NCT03390296 [106] | I/II | 21 | Completed | R/R | - gemtuzumab ozogamicin on D8 - SC or IV AZA on D1–D7 or D1–D5 + D8–D9 - oral VEN on D1–D21 | |
cusatuzumab (anti-CD70) + AZA + VEN | NCT04150887 (ELEVATE) [115] | I | 61 | Not Recruiting | N/D | - unfit for intensive chemotherapy - IV cusatuzumab on D3 and D17 | |
NCT06384261 (OV-AML-1231) | II | 120 | Not Recruiting | N/D | - unfit for intensive chemotherapy - IV cusatuzumab on D3 and D17 - direct comparison to AZA + VEN alone | ||
aplitabart (anti-DR5) + VEN | NCT04553692 | I | 430 | Recruiting | N/D R/R | - death receptor 5-targeted therapy | |
NP137 + AZA + VEN | NCT06150040 | I/II | 35 | Recruiting | R/R | - nectin-1 directed therapy | |
Antibody- drug conjugate | tagraxofusp (SL-401) (anti-CD123) + AZA + VEN | NCT03113643 [118] | I | 72 | Recruiting | N/D R/R | - adverse risk AML - unfit for intensive chemotherapy - CD123-directed therapy - IV tagraxofusp on D1–D3 or D1–D5 - IV AZA on D1–D7 - oral VEN on D1–D21 |
tagraxofusp (SL-401) (anti-CD123) + AZA + VEN | NCT06456463 | II | 72 | Recruiting | N/D | - unfit for intensive chemotherapy - CD123-directed therapy - IV tagraxofusp on D4–D6 - IV AZA on D1–D7 - oral VEN on D1–D28 | |
pivekumab sunirine (IMGN632) + AZA + VEN | NCT04086264 [119] | I/II | 218 | Not Recruiting | N/D R/R | - CD123-directed therapy - both fit and unfit patients eligible - 21-day cycles - IMGN632 administered on D7 of each cycle | |
lintuzumab- Ac225 + VEN | NCT03867682 [117] | I/II | 38 | Recruiting | R/R | - CD33-directed therapy - lintuzumab-Ac225 on D5 for 4 cycles - oral VEN on D1–D21 for 12 cycles - 28-day cycles with expansion to 42 days in case of cytopenias | |
Natural Killer (NK)-cell Engagers | SAR443579 + AZA + VEN | NCT06508489 | I/II | 18 | Recruiting | N/D | - unfit for intensive chemotherapy - IV SAR443579 weekly - IV AZA on D1–D7 - oral VEN on D1–D28 |
Adoptive Cellular Therapies | cytokine-induced memory-like NK-cells + VEN | NCT06152809 | I | 10 | Not Recruiting | N/D | - patients with adverse risk AML or mutations associated with VEN resistance - MRD+ patients in CR are eligible - safety assessment |
allogeneic NK-cells + AZA + VEN | NCT05834244 (ADVENT-AML) | I | 32 | Recruiting | R/R | - patients with adverse risk AML - unfit for intensive chemotherapy and HSCT |
