Select targeted T-cell therapies currently in MDS clinical trials
| Therapy . | Target . | Phase . | Enrolled patients . | Response rate OS rate and mOS . | AEs grade ≥3 . | NCT number/reference . |
|---|---|---|---|---|---|---|
| Immune checkpoint inhibitors | ||||||
| Pembrolizumab | PD-1 | 1b | N = 28 lower- and higher-risk MDS (HMA failure) | Overall ORR: 0% SD: 44% mOS: 6 mo 2-y OS (overall): 17% 2-y OS (intermediate-1): 46% 2-y OS (intermediate-2 and higher-risk): 0% | Gastro-enteritis: 4% Pain: 4% TLS: 4% | NCT01953692100 |
| Pembrolizumab + azacytidine | PD-1 | 2 | N = 37 20 HMA failure n = 17 frontline | HMA-refractory ORR: 25% CR: 5% mCR: 10% HI: 10% mOS: 5.8 mo Frontline cohort ORR: 76% CR: 18% mCR: 29% HI: 6% mOS: not reached (mFU: 12.8 mo) | Neutropenia: 32% Pneumonia: 24% FN: 18% Anemia: 12% | NCT03094637101 |
| Nivolumab and/or ipilimumab ± azacytidine | PD-1 (Nivo) CTLA-4 (Ipi) | 2 | N = 76 n = 35 HMA-failure n = 41 frontline | ORR: 13% (Nivo; HMA-failure) ORR: 35% (Ipi; HMA-failure) ORR: 75% (Nivo + Aza; frontline) ORR: 71% (Ipi + aza; frontline) CR/CRp: 15% (Nivo; HMA-failure) CR/CRp: 0% (Ipi; HMA-failure) CR/CRp: 50% (Nivo + Aza; frontline) CR/CRp: 38% (Ipi + Aza; frontline) mOS: 8 mo (Ipi or Nivo; HMA-failure) mOS: not reached (Ipi + Aza; frontline) mOS: 12 mo (Nivo + Aza; frontline) | NS | NCT02530463102 |
| Nivolumab and ipilimumab ± azacytidine | PD-1 (Nivo) CTLA-4 (Ipi) | Basket exploratory phase 2 | N = 26 n = 11 HMA-failure n = 15 frontline | Ipi + Nivo (HMA-refractory cohort) ORR: 36% CR: 9%; CRi: 9% HI: 18% mPFS: 7.1 mo mOS: 11.4 mo Ipi + Nivo + Aza (frontline cohort) ORR: 67% CR: 5% HI: 5% mPFS: 10 mo mOS: 12 mo | Infection: 55% FN: 46% Rash: 24% Elevated AST/ALT: 24% | NCT02530463103 |
| Sabatolimab + HMAs | TIM-3 | 1b | 53 MDS | ORR: 57% mDOR: 16.1 mo | Neutropenia: 47% Thrombocytopenia: 43% FN: 36% Anemia: 28% | NCT03066648104 |
| Sabatolimab + HMAs | TIM-3 | 2 | N = 65 higher-risk MDS | Overall ORR: 68% CR: 22% mOS: 22.8 mo mPFS: 11.1 mo | Neutropenia: 56% Thrombocytopenia: 37% FN: 35% Anemia: 23% Leukopenia: 23% | NCT03946670105 |
| Adoptive T-cell therapies | ||||||
| CYAD-01 | NKG2D-based CAR T cells | 1 | 22 total 1 R/R MDS | Patient achieved mCR | CRS: 31% Lymphopenia: 19% | NCT03018405106 |
| PRGN-3006 Ultra CAR T cells | CD33 | 1/1b | N = 24 n = 3 R/R MDS n = 1 CMML n = 20 R/R AML | ORR MDS/CMML: 0% ORR (AML): 30% (1 CRi, 1 CRh, 1 PR) | Transient CRS grade 3 | NCT03927261107 |
| Bispecific antibodies | ||||||
| Flotetuzumab | CD3 + CD123 | 1/2 | N = 5 R/R MDS | 1 evaluable patient: PD | No results reported | NCT02152956108,109 |
| APVO436 | CD3 + CD123 | 1b | N = 46 n = 39 R/R AML n = 7 R/R MDS | patients with MDS NE: 1 SD: 3 mCR: 3 | CRS: 8.7% Anemia: 4.3% IRR: 4.3% | NCT03647800110 |
| Vibecotamab | CD3 + CD123 | 2 | 23 total 9 R/R MDS 12 AML 2 CMML | mCR + HI: 44% HI: 11% CRL: 56% | Infusion reaction: 4% | NCT05285813111 |
| JNJ-67571244 | CD3 + CD33 | 1 | N = 68 R/R HR-MDS R/R AML | No results reported | No results reported | NCT03915379112 |
| AMV564 | CD3 + CD33 | 1 | N = 14 | No reported results | No results reported | NCT03516591113 |
| Therapy . | Target . | Phase . | Enrolled patients . | Response rate OS rate and mOS . | AEs grade ≥3 . | NCT number/reference . |
|---|---|---|---|---|---|---|
| Immune checkpoint inhibitors | ||||||
| Pembrolizumab | PD-1 | 1b | N = 28 lower- and higher-risk MDS (HMA failure) | Overall ORR: 0% SD: 44% mOS: 6 mo 2-y OS (overall): 17% 2-y OS (intermediate-1): 46% 2-y OS (intermediate-2 and higher-risk): 0% | Gastro-enteritis: 4% Pain: 4% TLS: 4% | NCT01953692100 |
| Pembrolizumab + azacytidine | PD-1 | 2 | N = 37 20 HMA failure n = 17 frontline | HMA-refractory ORR: 25% CR: 5% mCR: 10% HI: 10% mOS: 5.8 mo Frontline cohort ORR: 76% CR: 18% mCR: 29% HI: 6% mOS: not reached (mFU: 12.8 mo) | Neutropenia: 32% Pneumonia: 24% FN: 18% Anemia: 12% | NCT03094637101 |
| Nivolumab and/or ipilimumab ± azacytidine | PD-1 (Nivo) CTLA-4 (Ipi) | 2 | N = 76 n = 35 HMA-failure n = 41 frontline | ORR: 13% (Nivo; HMA-failure) ORR: 35% (Ipi; HMA-failure) ORR: 75% (Nivo + Aza; frontline) ORR: 71% (Ipi + aza; frontline) CR/CRp: 15% (Nivo; HMA-failure) CR/CRp: 0% (Ipi; HMA-failure) CR/CRp: 50% (Nivo + Aza; frontline) CR/CRp: 38% (Ipi + Aza; frontline) mOS: 8 mo (Ipi or Nivo; HMA-failure) mOS: not reached (Ipi + Aza; frontline) mOS: 12 mo (Nivo + Aza; frontline) | NS | NCT02530463102 |
| Nivolumab and ipilimumab ± azacytidine | PD-1 (Nivo) CTLA-4 (Ipi) | Basket exploratory phase 2 | N = 26 n = 11 HMA-failure n = 15 frontline | Ipi + Nivo (HMA-refractory cohort) ORR: 36% CR: 9%; CRi: 9% HI: 18% mPFS: 7.1 mo mOS: 11.4 mo Ipi + Nivo + Aza (frontline cohort) ORR: 67% CR: 5% HI: 5% mPFS: 10 mo mOS: 12 mo | Infection: 55% FN: 46% Rash: 24% Elevated AST/ALT: 24% | NCT02530463103 |
| Sabatolimab + HMAs | TIM-3 | 1b | 53 MDS | ORR: 57% mDOR: 16.1 mo | Neutropenia: 47% Thrombocytopenia: 43% FN: 36% Anemia: 28% | NCT03066648104 |
| Sabatolimab + HMAs | TIM-3 | 2 | N = 65 higher-risk MDS | Overall ORR: 68% CR: 22% mOS: 22.8 mo mPFS: 11.1 mo | Neutropenia: 56% Thrombocytopenia: 37% FN: 35% Anemia: 23% Leukopenia: 23% | NCT03946670105 |
| Adoptive T-cell therapies | ||||||
| CYAD-01 | NKG2D-based CAR T cells | 1 | 22 total 1 R/R MDS | Patient achieved mCR | CRS: 31% Lymphopenia: 19% | NCT03018405106 |
| PRGN-3006 Ultra CAR T cells | CD33 | 1/1b | N = 24 n = 3 R/R MDS n = 1 CMML n = 20 R/R AML | ORR MDS/CMML: 0% ORR (AML): 30% (1 CRi, 1 CRh, 1 PR) | Transient CRS grade 3 | NCT03927261107 |
| Bispecific antibodies | ||||||
| Flotetuzumab | CD3 + CD123 | 1/2 | N = 5 R/R MDS | 1 evaluable patient: PD | No results reported | NCT02152956108,109 |
| APVO436 | CD3 + CD123 | 1b | N = 46 n = 39 R/R AML n = 7 R/R MDS | patients with MDS NE: 1 SD: 3 mCR: 3 | CRS: 8.7% Anemia: 4.3% IRR: 4.3% | NCT03647800110 |
| Vibecotamab | CD3 + CD123 | 2 | 23 total 9 R/R MDS 12 AML 2 CMML | mCR + HI: 44% HI: 11% CRL: 56% | Infusion reaction: 4% | NCT05285813111 |
| JNJ-67571244 | CD3 + CD33 | 1 | N = 68 R/R HR-MDS R/R AML | No results reported | No results reported | NCT03915379112 |
| AMV564 | CD3 + CD33 | 1 | N = 14 | No reported results | No results reported | NCT03516591113 |
AEs, adverse effects; Aza, azacytidine; CMML, chronic myelomonocytic leukemia; CRh, complete response with complete cytogenetic remission; CRi, complete response with incomplete count recovery; CRp, complete remission with incomplete platelet recovery; CRS, cytokine release syndrome; DOR, duration of response; FN, febrile neutropenia; HI, hematological improvement; HR, higher-risk; Ipi, ipilimumab; IRR, infusion-related reaction; mCR, marrow complete response; mFU, median follow-up; mOS, median overall survival; PR, partial response; mPFS, median progression-free-survival; NA, not available; NE, not evaluable; Nivo, nivolumab; ORR, overall response rate; OS, overall survival; PD, progressive disease; RFS, relapse-free survival; SD, stable disease; TLS, tumor lysis.