Table 4 Venetoclax and targeted therapy combinations for acute myeloid leukemia.
Drug class combined with VEN | Drug combination | NCT ID | Phase | N | Status | Patient population | Regimen |
|---|---|---|---|---|---|---|---|
FLT3- inhibitors | gilteritinib + VEN | I | 61 | Completed | R/R | - FLT3mut AML - 120 mg oral gilteritinib on D1–D28 - 400 mg oral VEN on D1–D28 - pharmacokinetic analysis | |
gilteritinib + AZA + VEN | NCT05520567 [64] | I/II | 70 | Recruiting | N/D | - FLT3mut AML (ITD or D835 - elderly patients (>75 years old) unfit for intensive chemotherapy - assessment of the safety of the triplet - oral 80 mg gilteritinib on D1–D28 - IV or SC 75 mg/m2 AZA on D1–D7 - oral 400 mg VEN on D1–D28 with a 3-day dose ramp up | |
gilteritinib + AZA + VEN | NCT04140487 [62] | I/II | 55 | Not Recruiting | N/D R/R | - FLT3mut AML (ITD or D835) - patients 18 years or older unfit for intensive chemotherapy - up to 24 cycles - oral AZA once daily on D1–D7 - oral 400 mg VEN once daily on D1–D28 with a 3-day dose ramp up - oral 80 mg gilteritinib once daily on D1–D28 | |
gilteritinib + AZA + VEN | NCT06317649 (Myelomatch MM1OA-EA02) [66] | II | 147 | Recruiting | N/D | - comparison of 80 mg oral gilteritinib once daily on D1–D28 versus D8-D21 - FLT3mut AML (ITD or D835) - elderly patients (>75 years old) unfit for intensive chemotherapy - two cycles of induction and maintenance up to 2 years with the same regimen - IV or SC AZA once daily on D1–D7 - oral 400 mg VEN once daily on D1–D28 with a 3-day dose ramp up | |
gilteritinib + DEC + VEN | NCT03013998 (Beat AML S8) [64] | I/II | 17 | Recruiting | N/D | - patients aged >60 years, unfit for intensive chemotherapy - oral 80 mg gilteritinib on D1–D28 seemed the best, but multiple dose-levels have been tested - IV 20 mg/m2 DEC on D8–D1 - oral VEN 400 mg on D1–D28 | |
gilteritinib + ASTX727 (oral DEC) + VEN | NCT05010122 | I/II | 42 | Recruiting | N/D R/R | - FLT3mut AML (ITD or D835) - 24 cycles + gilteritinib maintenance - oral ASTX727 once daily on D1–D5 - oral VEN once daily on D1–D21 - oral gilteritinib once daily on D1–D28 | |
quizartinib + AZA + VEN (VEN-A-QUI) | NCT04687761 | I/II | 84 | Recruiting | N/D | - unfit for intensive chemotherapy - regardless of FLT3 mutational status - SC or IV AZA 75 mg/m2, once daily on D1–D5 and D8-9 (5 “on”, 2 “off”, 2 “on) - oral VEN once daily on D1–D28 - oral quizartinib once daily on D1–D5 | |
quizartinib + DEC + VEN | NCT03661307 [68] | I/II | 73 | Recruiting | N/D R/R | - FLT3-ITD mutant AML - two cycles - IV DEC once daily on D1–D10 - oral VEN once daily on D1–D14 - oral quizartinib once daily on D1–D28 | |
tuspetinib +VEN + - AZA | NCT03850574 | I/II | 218 | Recruiting | R/R | - safety assessment | |
IDH1/2 -inhibitors | ivosidenib + AZA + VEN | NCT03471260 [73] | I/II | 96 | Recruiting | N/D R/R | - IDH1m AML (R132) - unfit for intensive chemotherapy - SC AZA once daily on D1–D7 - oral VEN once daily on D1–D14 - oral ivosidenib once daily on D15–D28 |
enasidenib + VEN | NCT04092179 [75] | I/II | 27 | Completed | R/R | - IDH2m AML (R140 or R172) - oral VEN once daily on D1–D28 - oral enasidenib once daily on D15–D28 - cycles continue until disease progression or intolerable toxicities | |
ivosidenib or enasidenib + ASTX727 (oral DEC) + VEN | NCT04774393 [76] | I/II | 84 | Recruiting | R/R | - unfit for intensive chemotherapy - bilineage leukemia or isolated extramedullary AML also eligible - oral ASTX727 once daily on D1–D5 - oral VEN once daily on D1–D14 - oral ivosidenib or enasidenib on D1–D28 - cycles continue until disease progression or intolerable toxicities | |
enasidenib + ASTX727 + VEN (MyeloMatch subtrial) | NCT06672146 | II | 93 | Not yet recruiting | N/D | - unfit for intensive chemotherapy - oral enasidenib once daily on D1–D28 - oral ASTX727 once daily on D1–D5 - oral VEN once daily on D1–D28 | |
olutasidenib + DEC + VEN | NCT06445959 | I/II | Recruiting | N/D R/R | - unfit for intensive chemotherapy - safety and pharmacokinetic assessment | ||
crelosidenib (LY3410738, dual IDH1/IDH2 inhibitor) + AZA + VEN | NCT04603001 | I | 260 | Not Recruiting | N/D R/R | - IDH1 R132, IDH2 R140 or IDH2 R172 mutated AML - 75 years or older, unfit for intensive chemotherapy - safety and pharmacokinetic assessment | |
enasidenib + AZA versus AZA + VEN | NCT05401097 (I-DATA) [72] | II | 125 | Recruiting | N/D | - sequential IDH-inhibitor + AZA followed by AZA + VEN versus AZA + VEN followed by IDH-inhibitor + AZA - CR has to be reached in 3 AZA + VEN cycles and 5 IDH-inhibitor + AZA cycles - SC AZA once daily on D1–D5 for up to 6 cycles - oral, once daily VEN on D1–D28 for up to 24 cycles | |
Menin -inhibitors | revumenib + VEN | NCT06284486 [83] | II | 8 | Recruiting | N/D | - efficacy of revumenib + VEN in clearance of MRD following high-intensity or low-intensity therapies - NPM1mt, or KMT2Ar, or NUP98r AML in CR with MRD ≥ 0.1% - oral VEN once daily on D1–D14 - oral revumenib once daily on D1–D18 - cycles continue until disease progression or intolerable toxicities |
revumenib + AZA + VEN | NCT06177067 | I | 24 | Recruiting | R/R | - KMT2A, NUP98, NPM1-mutated AML - age ≤30 years | |
revumenib + ASTX7272 (oral DEC) + VEN | NCT05360160 (SAVE) [80] | I/II | 43 | Recruiting | N/D R/R | - KMT2Ar, or NUP98r, or NPM1-mutated AML - unfit for intensive chemotherapy - oral revumenib twice daily on D1–D28 - oral ASTX727 once daily on D1–D5 - oral VEN once daily on D1–D14 | |
ziftomenib + AZA + VEN | NCT05735184 (KOMET-007) [78] | I | 212 | Recruiting | N/D R/R | - comparison of 7 + 3 + ziftomenib versus ziftomenib + AZA + VEN in N/D patients - KMT2A, NPM1-mutated AML - young patients also included - oral revumenib on D8-D28 in cycle 1, D1–D28 in the other cycles - IV or SC AZA on D1–D5 - oral VEN on D1–D28 | |
NCT06397027 (ZiVa) [79] | I | 22 | Not yet recruiting | R/R | - pediatric and young adult patients (2–21 years) - oral revumenib on D8-D28 in cycle 1, D1–D28 in the other cycles - IV or SC AZA on D1–D5 - oral VEN on D1–D14 | ||
bleximenib (JNJ-75276617) + AZA + VEN | NCT05453903 | I | 150 | Recruiting | R/R | - KMT2A, NPM1-mutated AML - secondary AML also accepted - safety assessment | |
emilumenib (DS-1594b) + AZA + VEN | NCT04752163 | I/II | 17 | Completed | R/R | - in arm A patients enrolled irrespective of mutational status - safety assessment | |
p53- reactivators and MDM2 antagonists | idasanutlin + VEN | NCT02670044 [85] | II | 88 | Completed | R/R | - unfit for intensive chemotherapy - oral idasanutlin on D1–D5 - oral VEN on D1–D28 |
NCT04029688 | I/II | 38 | Completed | R/R | - young adults (age <30 years) - oral idasanutlin on D1–D5 - oral VEN on D1–D28 | ||
navtemadlin + DEC + VEN | NCT03041688 | I | 58 | Recruiting | R/R | - wild-type TP53, adverse risk AML - 4 cycles of induction then maintenance - oral navtemadlin on D1–D7 in both induction and maintenance - IV DEC on D1–D10 in induction and D1–D5 in maintenance - oral VEN on D1–D21 in induction and D1–D14 in maintenance | |
siremadlin (HDM201) + VEN | NCT03940352 [86] | I | 52 | Not Recruiting | R/R | - wild-type TP53, adverse risk AML - unfit for intensive chemotherapy - safety and pharmacokinetics assessment - oral siremadlin on D1–D5 - IV or SC AZA on D1–D7 - oral VEN on D1–D28 | |
siremadlin (HDM201) + AZA + VEN | NCT05155709 [87] | I | 14 | Not Recruiting | N/D | - wild-type TP53, adverse risk AML - unfit for intensive chemotherapy - safety and pharmacokinetics assessment - oral siremadlin on D1–D5 - IV or SC AZA on D1–D7 - oral VEN on D1–D28 | |
eprenetapropt + AZA + VEN | NCT04214860 [88] | I | 51 | Completed | R/R | - TP53-mutated AML - oral eprenetapropt on D1–D4 - IV or SC AZA on D1–D7 - oral VEN on D1–D28 | |
Cyclin -dependent kinase (CDK) -inhibitors | alvocidib + VEN | NCT03441555 [90] | I | 36 | Completed | R/R | - IV alvocidib on D1–D3 - oral VEN on D1–D28 - safety and pharmacokinetics assessment |
fadraciclib + VEN | NCT04017546 | I | 14 | Completed | R/R | - safety and pharmacokinetics assessment | |
voruciclib + VEN | NCT03547115 [91] | I | 100 | Recruiting | R/R | - safety and pharmacokinetics assessment | |
QHRD107 + AZA + VEN | NCT06532058 [92] | I | 53 | Recruiting | R/R | - safety and pharmacokinetics assessment | |
RVU120 + AZA + VEN | NCT06191263 (RIVER-81) | II | 98 | Recruiting | R/R | - 21-day cycles - oral RV120 on D1–D13 - SC or IV AZA on D1–D7 - oral VEN on D1–D14 - safety and pharmacokinetics assessment | |
SLS009 (GFH009) + AZA + VEN | NCT04588922 | I/II | 135 | Recruiting | R/R | - adverse risk, ASXL1, BCOR, EZH2, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 mutated AML - safety and pharmacokinetics assessment - IV SLS009 twice a week - SC or IV AZA on D1–D7 - oral VEN on D1–D28 | |
HC-7366 + AZA + VEN | NCT06285890 | I | 18 | Not Recruiting | R/R | - GCN2 (general control nonderepressible 2) kinase inhibitor - safety and pharmacokinetics assessment - oral HC-7366 on D1–D28 - SC or IV AZA on D1–D7 - oral VEN on D1–D28 | |
Cerebron ligase inhibitors | selinexor + VEN | NCT03955783 | I | 78 | Completed | R/R | - adverse risk AML - oral selinexor on D1, D8, D15, D22 - oral VEN on D1–D28 |
selinexor + AZA + VEN | NCT05736965 [94] | II | 58 | Recruiting | N/D | - unfit for intensive chemotherapy - oral selinexor on D3, D10, D17 - SC or IV AZA on D1–D3, D8–D9, D15–D16 - oral VEN on D3–D14 | |
selinexor + AZA + VEN | NCT05736978 | II | 58 | Recruiting | N/D | - unfit for intensive chemotherapy - patients will get selinexor based on MRD-results on D14 - oral selinexor on D15 and D22 | |
eltanexor + VEN | NCT06399640 | I | 60 | Not Recruiting | R/R | - eltanexor 5 days a week for 14, 21, or 28 days - oral VEN on D1–D14 | |
regorafenib + AZA + VEN | NCT06454409 | I/II | 20 | Not Recruiting | R/R | - multi-kinase inhibitor - unfit for intensive chemotherapy - 12 cycles - oral regorafenib on D1–D21 - IV AZA on D1–D7 - oral VEN on D1–D21 | |
trametinib + AZA + VEN | NCT04487106 [96] | II | 21 | Completed | N/D R/R | -MEK-inhibitor - unfit for intensive chemotherapy - 24 cycles - oral trametinib on D1–D28 - SC or IV AZA on D1–D7 - oral VEN on D1–D21 | |
cobimetinib + VEN | NCT02670044 [97] | II | 88 | Completed | R/R | - MEK-inhibitor - unfit for intensive chemotherapy - oral cobimetinib on D1–D28 - oral VEN on D1–D21 | |
mivebresib + VEN | NCT02391480 [98] | I | 128 | Completed | R/R | - BET-inhibitor | |
emavusertib + VEN | NCT04278768 [101] | I/II | 336 | Recruiting | R/R | - IRAK4-inhibitor - FLT3m, SF3B1 or U2AF1 mutated AML - oral emavusertib on D1–D21 - oral VEN on D1–D21 - 28-day cycles | |
cirtuvivint + ASTX727 (oral DEC) + VEN | NCT06484062 | I | 48 | Not Recruiting | R/R | - CDC-like kinase (CLK) inhibitor. | |
CCS1477 (inobrodib) + AZA + VEN | NCT04068597 | I/II | 250 | Recruiting | R/R | - EP300/CBP bromodomain inhibitor | |
danvatirsen + VEN | NCT05986240 | I | 24 | Recruiting | R/R | - STAT-inhibitor | |
OPB-111077 + DEC + VEN | NCT03063944 [104] | I | 37 | Completed | N/D R/R | - STAT-inhibitor - unfit for intensive chemotherapy - OPB-111077 on D1–D28 - IV DEC on D4–D8 - oral VEN on D4–D28 |
