Selected ongoing trials of immune checkpoint agents in NHL
| . | Immune checkpoint and drug . | Other combination partner . | Disease . | Clinical setting . | Phase . | Number of patients . | NCT Number . |
|---|---|---|---|---|---|---|---|
| Initial treatment in DLBCL | PD-L1 (avelumab) | RCHOP | DLBCL | Untreated stage II-IV | 1 | 28 | NCT03244176 |
| PD-L1 (durvalumab) | RCHOP or RCHOP + lenalidomide | DLBCL | Untreated | 2 | 120 | NCT03003520 | |
| Combination checkpoint agents in DLBCL | PD-L1 (avelumab) + 4-1BB (utomilumab) | Rituximab or azacitade or bendamustine | DLBCL | R/R | 1b | 304 | NCT02951156 |
| PD-1 (nivolumab) + CD27 (varilumab) | NA | DLBCL | R/R | 2 | 106 | NCT03038672 | |
| DLBCL subtypes with 9p24.1 alterations | PD-L1 (durvalumab) | Lenalidomide | DLBCL subtypes (EBV positive, PCNSL, PTL) | R/R | 2 | 21 | NCT03212807 |
| PD-1 (nivolumab) | NA | PCNSL/PTL | R/R | 2 | 65 | NCT02857426 | |
| PD-1 (pembrolizumab) | NA | PCNSL | R/R | 2 | 21 | NCT02779101 | |
| Combinations including anti-CD20 agents in B-cell NHLs | PD-1 (pembrolizumab) | Rituximab | FL | R/R | 2 | 30 | NCT02446457 |
| PD-L1 (atezolizumab) | Obinutuzumab or tazemetostat | DLBCL or FL | R/R | 1 | 92 | NCT02220842 | |
| PD-L1 (atezolizumab) | Polatuzumab vedotin and rituximab or obinutuzumab | DLBCL or FL | R/R | 1 | 92 | NCT02729896 | |
| PD-L1 (atezolizumab) | Obinutuzumab and lenalidomide | DLBCL or FL | R/R | 1 | 46 | NCT02631577 | |
| PD-L1 (atezolizumab) | Obinutuzumab and bendamustine or obinutuzumab and CHOP | DLBCL or FL | R/R or untreated | 1b/2 | 92 | NCT02596971 | |
| Other combinations in B-cell NHL | PD-1 (nivolumab) | Brentuximab | CD30+ NHL | R/R | 1/2 | 146 | NCT02581631 |
| PD-1 (pembrolizumab) | Intratumoral G100 (TLR-4 agonist) | FL or MZL | R/R | 1/2 | 65 | NCT02501473 | |
| PD-1 (pembrolizumab) | Lenalidomide | Lymphoma | R/R | 1/2 | 29 | NCT02875067 | |
| PD-1 (nivolumab) | Lenalidomide | NHL or cHL | R/R | 1/2 | 102 | NCT03015896 | |
| PD-1 (pembrolizumab) | Ibrutinib | B cell NHL | R/R | 1 | 58 | NCT02950220 | |
| PD-1 (pembrolizumab) | EBRT (20-50 Gy) | NHL | R/R | 2 | 70 | NCT03210662 | |
| PD-1 (pembrolizumab) | Dendritic cell therapy, cryoablation | NHL | R/R | 1/2 | 44 | NCT03035331 | |
| PD-1 (pembrolizumab) | Entinostat (HDAC inhibitor) | FL or cHL | R/R | 2 | 78 | NCT03179930 | |
| PD-1 (pembrolizumab) | Vorinostat (HDAC inhibitor) | cHL, DLBCL, or FL | R/R | 1 | 60 | NCT03150329 | |
| Combination studies in CLL | |||||||
| PD-1 (pembrolizumab) | Ibrutinib | CLL or MCL | R/R | 1/2 | 40 | NCT03153202 | |
| PD-1 (nivolumab) | Ibrutinib | CLL | R/R | 2 | 72 | NCT02420912 | |
| PD-L1 (atezolizumab) | Obinutuzumab and ibrutinib | CLL | R/R or high-risk untreated | 2 | 72 | NCT02846623 | |
| PD-L1 (durvalumab) | Lenalidomide + rituximab or ibrutinib or bendamustine + rituximab | Lymphoma, CLL | R/R | 1/2 | 253 | NCT02733042 | |
| PD-1 (pembrolizumab) | Ibrutinib and fludarabine | CLL | R/R | 2 | 30 | NCT03204188 | |
| PD-1 (pembrolizumab) | Ublituximab and TGR-1202 (PI3K δ inhibitor) | CLL or RT | R/R | 1/2 | 12 | NCT02535286 | |
| PD-1 (pembrolizumab) | Ibrutinib or idelalisib | CLL or indolent B cell lymphomas | R/R | 2 | 68 | NCT02332980 | |
| Trials in TCLs | PD-L1 (avelumab) | NA | PTCL | R/R | 2 | 35 | NCT03046953 |
| PD-1 (nivolumab) | NA | PTCL | R/R | 2 | 39 | NCT03075553 | |
| ICOS (MEDI-570) | NA | PTCL (follicular variant) or AITL | R/R | 1 | 46 | NCT02520791 | |
| PD-L1 (durvalumab) | Lenalidomide | PTCL | R/R | 1/2 | 62 | NCT03011814 | |
| PD-L1 (durvalumab) | Lenalidomide | NK/T cell lymphoma | R/R | 2 | 22 | NCT03054532 | |
| PD-L1 (durvalumab) | Combinations of pralatrexate, romidepsin, and/or azacitadine | PTCL | R/R | 1/2 | 148 | NCT03161223 | |
| PD-L1 (durvalumab) | Radiation | CTCL | Untreated or R/R | 1 | 19 | NCT03235869 | |
| PD-1 (pembrolizumab) | Decitabine and pralatrexate | PTCL and CTCL | R/R | 1 | 42 | NCT03240211 | |
| Consolidation after ASCT | PD-1 (nivolumab) + CTLA-4 (ipilimumab) | NA | Lymphoma | Consolidation following ASCT | 1/2 | 42 | NCT02681302 |
| PD-1 (pembrolizumab) | NA | DLBCL, cHL, PTCL | Consolidation following ASCT | 2 | 60 | NCT02362997 | |
| PD-L1 (durvalumab) | NA | DLBCL | Consolidation following ASCT | 2 | 46 | NCT03241017 | |
| Combination with CAR-T cells | |||||||
| PD-L1 (atezolizumab) | KTE-C19 | DLBCL | R/R | 1/2 | 31 | NCT02926833 | |
| PD-L1 (durvalumab) | JCAR014 | DLBCL | R/R | 1 | 42 | NCT02706405 | |
| PD-1 (pembrolizumab) | NA | CD19+ DLBCL, MCL, FL | Relapse after anti-CD19 CAR T-cell therapy | 1/2 | 12 | NCT02650999 |
| . | Immune checkpoint and drug . | Other combination partner . | Disease . | Clinical setting . | Phase . | Number of patients . | NCT Number . |
|---|---|---|---|---|---|---|---|
| Initial treatment in DLBCL | PD-L1 (avelumab) | RCHOP | DLBCL | Untreated stage II-IV | 1 | 28 | NCT03244176 |
| PD-L1 (durvalumab) | RCHOP or RCHOP + lenalidomide | DLBCL | Untreated | 2 | 120 | NCT03003520 | |
| Combination checkpoint agents in DLBCL | PD-L1 (avelumab) + 4-1BB (utomilumab) | Rituximab or azacitade or bendamustine | DLBCL | R/R | 1b | 304 | NCT02951156 |
| PD-1 (nivolumab) + CD27 (varilumab) | NA | DLBCL | R/R | 2 | 106 | NCT03038672 | |
| DLBCL subtypes with 9p24.1 alterations | PD-L1 (durvalumab) | Lenalidomide | DLBCL subtypes (EBV positive, PCNSL, PTL) | R/R | 2 | 21 | NCT03212807 |
| PD-1 (nivolumab) | NA | PCNSL/PTL | R/R | 2 | 65 | NCT02857426 | |
| PD-1 (pembrolizumab) | NA | PCNSL | R/R | 2 | 21 | NCT02779101 | |
| Combinations including anti-CD20 agents in B-cell NHLs | PD-1 (pembrolizumab) | Rituximab | FL | R/R | 2 | 30 | NCT02446457 |
| PD-L1 (atezolizumab) | Obinutuzumab or tazemetostat | DLBCL or FL | R/R | 1 | 92 | NCT02220842 | |
| PD-L1 (atezolizumab) | Polatuzumab vedotin and rituximab or obinutuzumab | DLBCL or FL | R/R | 1 | 92 | NCT02729896 | |
| PD-L1 (atezolizumab) | Obinutuzumab and lenalidomide | DLBCL or FL | R/R | 1 | 46 | NCT02631577 | |
| PD-L1 (atezolizumab) | Obinutuzumab and bendamustine or obinutuzumab and CHOP | DLBCL or FL | R/R or untreated | 1b/2 | 92 | NCT02596971 | |
| Other combinations in B-cell NHL | PD-1 (nivolumab) | Brentuximab | CD30+ NHL | R/R | 1/2 | 146 | NCT02581631 |
| PD-1 (pembrolizumab) | Intratumoral G100 (TLR-4 agonist) | FL or MZL | R/R | 1/2 | 65 | NCT02501473 | |
| PD-1 (pembrolizumab) | Lenalidomide | Lymphoma | R/R | 1/2 | 29 | NCT02875067 | |
| PD-1 (nivolumab) | Lenalidomide | NHL or cHL | R/R | 1/2 | 102 | NCT03015896 | |
| PD-1 (pembrolizumab) | Ibrutinib | B cell NHL | R/R | 1 | 58 | NCT02950220 | |
| PD-1 (pembrolizumab) | EBRT (20-50 Gy) | NHL | R/R | 2 | 70 | NCT03210662 | |
| PD-1 (pembrolizumab) | Dendritic cell therapy, cryoablation | NHL | R/R | 1/2 | 44 | NCT03035331 | |
| PD-1 (pembrolizumab) | Entinostat (HDAC inhibitor) | FL or cHL | R/R | 2 | 78 | NCT03179930 | |
| PD-1 (pembrolizumab) | Vorinostat (HDAC inhibitor) | cHL, DLBCL, or FL | R/R | 1 | 60 | NCT03150329 | |
| Combination studies in CLL | |||||||
| PD-1 (pembrolizumab) | Ibrutinib | CLL or MCL | R/R | 1/2 | 40 | NCT03153202 | |
| PD-1 (nivolumab) | Ibrutinib | CLL | R/R | 2 | 72 | NCT02420912 | |
| PD-L1 (atezolizumab) | Obinutuzumab and ibrutinib | CLL | R/R or high-risk untreated | 2 | 72 | NCT02846623 | |
| PD-L1 (durvalumab) | Lenalidomide + rituximab or ibrutinib or bendamustine + rituximab | Lymphoma, CLL | R/R | 1/2 | 253 | NCT02733042 | |
| PD-1 (pembrolizumab) | Ibrutinib and fludarabine | CLL | R/R | 2 | 30 | NCT03204188 | |
| PD-1 (pembrolizumab) | Ublituximab and TGR-1202 (PI3K δ inhibitor) | CLL or RT | R/R | 1/2 | 12 | NCT02535286 | |
| PD-1 (pembrolizumab) | Ibrutinib or idelalisib | CLL or indolent B cell lymphomas | R/R | 2 | 68 | NCT02332980 | |
| Trials in TCLs | PD-L1 (avelumab) | NA | PTCL | R/R | 2 | 35 | NCT03046953 |
| PD-1 (nivolumab) | NA | PTCL | R/R | 2 | 39 | NCT03075553 | |
| ICOS (MEDI-570) | NA | PTCL (follicular variant) or AITL | R/R | 1 | 46 | NCT02520791 | |
| PD-L1 (durvalumab) | Lenalidomide | PTCL | R/R | 1/2 | 62 | NCT03011814 | |
| PD-L1 (durvalumab) | Lenalidomide | NK/T cell lymphoma | R/R | 2 | 22 | NCT03054532 | |
| PD-L1 (durvalumab) | Combinations of pralatrexate, romidepsin, and/or azacitadine | PTCL | R/R | 1/2 | 148 | NCT03161223 | |
| PD-L1 (durvalumab) | Radiation | CTCL | Untreated or R/R | 1 | 19 | NCT03235869 | |
| PD-1 (pembrolizumab) | Decitabine and pralatrexate | PTCL and CTCL | R/R | 1 | 42 | NCT03240211 | |
| Consolidation after ASCT | PD-1 (nivolumab) + CTLA-4 (ipilimumab) | NA | Lymphoma | Consolidation following ASCT | 1/2 | 42 | NCT02681302 |
| PD-1 (pembrolizumab) | NA | DLBCL, cHL, PTCL | Consolidation following ASCT | 2 | 60 | NCT02362997 | |
| PD-L1 (durvalumab) | NA | DLBCL | Consolidation following ASCT | 2 | 46 | NCT03241017 | |
| Combination with CAR-T cells | |||||||
| PD-L1 (atezolizumab) | KTE-C19 | DLBCL | R/R | 1/2 | 31 | NCT02926833 | |
| PD-L1 (durvalumab) | JCAR014 | DLBCL | R/R | 1 | 42 | NCT02706405 | |
| PD-1 (pembrolizumab) | NA | CD19+ DLBCL, MCL, FL | Relapse after anti-CD19 CAR T-cell therapy | 1/2 | 12 | NCT02650999 |
AITL, angioimmunoblastic T cell lymphoma; CLL, chronic lymphocytic leukemia; EBRT, external beam radiation therapy; HDAC, histone deacetylase; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NA, not applicable; RCHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; PI3K, phosphatidylinositol 3-kinase; TLR, Toll-like receptor.