Table 1.
Clinical trials evaluating new drugs for patients with MDS.
| Agent | ClinicalTrials.gov identifier | Target | Phase | n | Population | Response outcomes | Survival outcomes | Reference |
|---|---|---|---|---|---|---|---|---|
| Guadecitabine | NCT02197676 | DNMT | II |
n = 49 (TN MDS) n = 53 (R/R MDS) |
HR MDS, low-blast AML, CMML | 37% CR + mCR 32% CR + mCR |
Median OS 23.4 months Median OS 11.7 months |
Garcia-Manero et al.19 |
| ASTX727 | NCT02103478 | DNMT | I | n = 43R/R MDS: 47% | MDS, CMML (TN and R/R) | ORR 32% 5 CR, 4 mCR, 5 HI |
NA | García-Manero et al.20 |
| Pembrolizumab | NCT01953692 | PD-1 | Ib | n = 28 | Monotherapy R/R hematologic malignancies | ORR 4%3 CR, 3 HI, 3 mCR, 1 PR | Median OS 23 weeks 2-year OS 49% |
García-Manero et al.25 |
| Nivolumab | NCT02530463 | PD-1 | II | n = 15 | Monotherapy R/R MDS Addition of azacitidine allowed after 4 cycles if NR |
ORR 13% | Median OS 8 months | García-Manero et al.26 |
| Ipilimumab | NCT02530463 | CTLA-4 | II | n = 39 | Monotherapy R/R MDS Addition of azacitidine allowed after 4 cycles if NR |
ORR 35% 3 CR, 3 clearance of mutations |
Median OS 8 months | García-Manero et al.26 |
| Nivolumab + ipilimumab | NCT02530463 | PD-1, CTLA-4 | II | n = 7 | R/R MDS Addition of azacitidine allowed after 4 cycles if NR |
ORR 39% 1 CR, 1 HI |
Median OS 8.4 months | García-Manero et al.27 |
| FT-2102 | NCT02719574 | IDH1 | I |
n = 2 (TN MDS) n = 4 (R/R MDS) |
AML/MDS with IDH mutation | ORR 25% 1 CR | NA | Watts et al.28 |
| Tomaralimab | NCT02363491 | TLR2 | I/II | n = 22 | LR MDS (>50% of patients had received ⩾4 previous therapies) | ORR 50%: 6 TI and 5 had reduction of need for transfusions |
NA | García-Manero et al.29,30 |
| Rigosertib | NCT02562443 | RAS, PI3K, PLK | III |
n = 299Rigosertib = 199 BSC = 100 |
HR R/R MDS | No significant differences in response | Median OS: –Global: 8.2 versus 5.9 months –Primary failure: 8.6 versus 5.3 months Very HR: 7.6 versus 3.2 months |
García-Manero et al.31 |
| Rigosertib + AZA | NCT01926587 | RAS, PI3K, PLK | II |
n = 14 (HMAN) n = 17 (HMA R/R) |
HR MDS, RAEB-t, nonproliferative AML | ORR: 79% (HMAN) 59% (HMA R/R) |
NA | Navada et al.32 |
AML, acute myeloid leukemia; AZA, azacitidine; BSC, best supportive care; CR, complete response; CMML, chronic myelomonocytic leukemia; DNMT, deoxyribonucleic acid methyltransferase; HI, hematological improvement; HMA, hypomethylating agent; HMAN, ; HR, high risk; IDH, isocitrate dehydrogenase; LR, low risk; mCR, marrow complete response; MDS, myelodysplastic syndrome; NA, not available; NR, not reached; ORR, objective response rate; OS, overall survival; PR, partial response; R/R, relapsed/refractory; RAEB-t, refractory anemia with excess blasts in transformation; TI, transfusion independence; TN, treatment naïve.