Drug | Mechanism of action and target | Combination | NCT | Patient population | Trial design | Outcomes | Status | References |
---|---|---|---|---|---|---|---|---|
Cedazuridine/decitabine | HMA with cytidine deaminase inhibitor | Monotherapy | NCT03306264 | N = 133 MDS and CMML | Phase III (ASCERTAIN) | PKs equivalence between oral and IV AUC 98.9% ORR: 61.7% CR: 22% mOS: 31.7 m LFS: 29.1 m | Completed | |
Cedazuridine/decitabine | HMA with cytidine deaminase inhibitor + BCL2 inhibitor | Venetoclax | NCT04655755 | N = 9 HR-MDS and CMML | Phase I | ORR: 100% CR: 67% with venetoclax 200 mg and 17% with venetoclax 400 mg | Ongoing | [30] |
Azacitidine | HMA + BCL2 inhibitor | Venetoclax | NCT02942290 | N = 51 receiving RP2D Untreated HR-MDS | Phase Ib | ORR: 84% CR: 40% mDoR: 13 m Time to CR: 2.6 m mOS in pts with CR: 28.6 m | Ongoing | [39] |
NCT04401748 | N = 500 Untreated HR-MDS | Phase III VERONA | No results yet | Ongoing | [40] | |||
NCT02966782 | N = 37 R/R HR-MDS | Phase Ib | ORR: 39% CR: 7% mDoR: 8.6 m mOS: 14.8 m | Ongoing | [42] | |||
APR-246 | TP53 inhibitor | Azacitidine | NCT03072043 | N = 40 MDS with at least one TP53 mutation | Phase II | ORR: 73% CR: 50% | Completed | [46] |
Azacitidine with or without APR-246 | NCT03745716 | N = 154 TP53-mutated MDS | Phase III | CR: 34.6% (APR-246) vs 22.4% (no APR-246) | Completed | [48] | ||
Pevonedistat | Inhibitor of the NEDD8-activating enzyme | With or without azacitidine | NCT02610777 | N = 120 HR-MDS, HR-CMML, and low-blasts AML | Phase II | ORR: 79% (comb) vs 57%, p = 0.065 CR: 52% (comb) vs 27%, p = 0.050 | Completed | [53] |
NCT03268954 | N = 454 HR-MDS, CMML, and low-blasts AML | Phase III (PANTHER) | CR: 24% (comb) vs 32% EFS: 17.7 (comb) vs 15.7 m, p = 0.557 | Completed | [54] | |||
Ivosidenib | IDH1 inhibitor | Monotherapy | NCT02074839 | Patients with hematologic malignancies N = 12 with R/R MDS | Phase I | ORR: 75% mDoR: 21.4 m | Ongoing | [55] |
NCT03503409 | N = 26 (A): failed HMA (B): untreated (C): low-risk MDS | Phase II IDIOME | ORR = 69% (A: 54%, B: 91%) CR = 46% (A: 23%: B: 73%) mDoR = 7.4 m mOS = 14 m (A: 7.7 m; B: not reached) | Ongoing | [56] | |||
Enasidenib | IDH2 inhibitor | Monotherapy | NCT01915498 | Patients with hematologic malignancies N = 17 with MDS | Phase I/II | Prior MDS treatment: ORR = 46% No prior MDS treatment: ORR = 75% (3/4) mDoR = 9 m mEFS: 11 m mOS: 16.9 m | Ongoing, close for recruitment | [57] |
With or without azacitidine | NCT03383575 | N = 21, R/R MDS N = 25, untreated MDS | Phase II | ORR: 84% (comb) vs 43% CR: 24% both arms mOS 32.2 m (comb) vs 21.3 m | Ongoing | [58] | ||
Emavusertib CA-4948 | IRAK4 inhibitor | With azacitidine | NCT04278768 | N = 43 R/R AML and HR-MDS | Phase I/IIa | Patients with MDS and SF3B1/U2AF1/FLT3 mutations: CR: 57% All patients without SF3B1/U2AF1/FLT3 mutations: CR: 1/29 (3.5%) | Ongoing |