Table 2.

Combination therapy with immune checkpoint inhibitors

AgentsMechanism of actionPhase of developmentCommentsReference
Nivolumab ipilimumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 2 Cohorts include single-agent immune checkpoint inhibitors and combination with azacitidine; MDS-HMA failure and naive NCT02530463 
Nivolumab azacitidine others* Immune checkpoint inhibitors plus DNMT inhibition Phase 2/3 Randomized phase 2, multiple experimental group study, selected exptal group in phase 2 proceeds to phase 3, azacitidine is the control group in both phase 2 and 3 NCT03092674 
Durvalumab CC-486 Immune checkpoint inhibitors plus DNMT inhibition Phase 2 MDS-HMA failure NCT02281084 
Durvalumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 2 Randomized phase 2, MDS, HMA naive-high or very high risk or intermediate risk with excess blasts or poor risk karyotype; AML ≥ 65 y old NCT02775903 
Pembrolizumab azacitidine* Immune checkpoint inhibitors plus DNMT inhibition Phase 2 MDS-HMA failure and naive cohorts, intermediate 1 or higher risk NCT03094637 
Nivolumab lirilumab azacitidine Anti-KIR MAB plus immune checkpoint inhibitors + DNMT inhibition Phase 2 Lirilumab + nivolumab in lower-risk MDS lirilumab + nivolumab + azacitidine in intermediate-2/high-risk MDS, HMA naive NCT02599649 
Atezolizumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 1 Single-agent immune checkpoint inhibitors or combination with azacitidine. MDS-HMA failure and HMA-naive cohorts NCT02508870 
Atezolizumab guadecitabine Immune checkpoint inhibitors plus DNMT inhibition Phase 1/2 MDS-HMA failure, intermediate-1 or higher-risk NCT02935361 
Ipilimumab decitabine Immune checkpoint inhibitors plus DNMT inhibition Phase 1 MDS-HMA failure and with excess blasts or MDS-relapsed after allo-HCT, AML R/R, or ≥75 y old; allo-HCT naive and allo-HCT failure cohorts NCT02890329 
Ipilimumab entinostat Immune checkpoint inhibitors plus HDAC inhibition Phase 1b MDS-HMA failure NCT02936752 
AgentsMechanism of actionPhase of developmentCommentsReference
Nivolumab ipilimumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 2 Cohorts include single-agent immune checkpoint inhibitors and combination with azacitidine; MDS-HMA failure and naive NCT02530463 
Nivolumab azacitidine others* Immune checkpoint inhibitors plus DNMT inhibition Phase 2/3 Randomized phase 2, multiple experimental group study, selected exptal group in phase 2 proceeds to phase 3, azacitidine is the control group in both phase 2 and 3 NCT03092674 
Durvalumab CC-486 Immune checkpoint inhibitors plus DNMT inhibition Phase 2 MDS-HMA failure NCT02281084 
Durvalumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 2 Randomized phase 2, MDS, HMA naive-high or very high risk or intermediate risk with excess blasts or poor risk karyotype; AML ≥ 65 y old NCT02775903 
Pembrolizumab azacitidine* Immune checkpoint inhibitors plus DNMT inhibition Phase 2 MDS-HMA failure and naive cohorts, intermediate 1 or higher risk NCT03094637 
Nivolumab lirilumab azacitidine Anti-KIR MAB plus immune checkpoint inhibitors + DNMT inhibition Phase 2 Lirilumab + nivolumab in lower-risk MDS lirilumab + nivolumab + azacitidine in intermediate-2/high-risk MDS, HMA naive NCT02599649 
Atezolizumab azacitidine Immune checkpoint inhibitors plus DNMT inhibition Phase 1 Single-agent immune checkpoint inhibitors or combination with azacitidine. MDS-HMA failure and HMA-naive cohorts NCT02508870 
Atezolizumab guadecitabine Immune checkpoint inhibitors plus DNMT inhibition Phase 1/2 MDS-HMA failure, intermediate-1 or higher-risk NCT02935361 
Ipilimumab decitabine Immune checkpoint inhibitors plus DNMT inhibition Phase 1 MDS-HMA failure and with excess blasts or MDS-relapsed after allo-HCT, AML R/R, or ≥75 y old; allo-HCT naive and allo-HCT failure cohorts NCT02890329 
Ipilimumab entinostat Immune checkpoint inhibitors plus HDAC inhibition Phase 1b MDS-HMA failure NCT02936752 

KIR, killer cell immunoglobulin-like receptor; MAB, monoclonal antibody.

*Not yet recruiting at time of manuscript submission.

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