Table 1 BCMA-targeted CAR-T clinical trials in multiple myeloma
From: Chimeric antigen receptor T cell therapies for multiple myeloma
Trial site/company | No. of patients | Costimulatory domain | Conditioning | Study design | Efficacy | Safety | Registration number/references |
|---|---|---|---|---|---|---|---|
National Cancer Institute, phase 1 | 24 | CD28 | CP/Flu | 0.3/1/3/9 × 106 CAR+T cells/kg | ORR, 20% (2 of 10) with 1 VGPR, 1 PR (lower doses) ORR, 86% (12 of 14) with 1 sCR, 8 VGPRs, 3 PRs (highest dose) | CRS: Gr3/4, none (lower doses) CRS: Gr3/4, 38% pts (highest dose) CRES: Gr3/4, 19% pts (highest dose) | |
Multisite phase 1, Bluebird (bb2121) | 33 | 4-1BB | CP/Flu | 50/150/450/800 × 106 CAR+T cells | ORR, 85% (28 of 33) with 12 sCRs, 3 CRs, 9 VGPRs, 4 PRs | CRS: Gr1/2, 70% pts; Gr3, 6% pts CRES: Gr1/2, 39% pts; Gr4, 3% pts | NCT02658929 [20] |
Multisite phase 1, Bluebird (bb21217) | 8 | 4-1BB | CP/Flu | 150/450/800/1200 × 106 CAR+T cells | ORR, 86%(6 of 7) with 1 sCR, 3 VGPRs, 2 PRs | CRS: Gr1/2, 50% pts; Gr3, 12.5% pts CRES: Gr4, 12.5% pts | NCT03274219 [23] |
Multisite phase1/2, Nanjing Legend, China (LCAR-B38M)(XJTU) | 57 | 4-1BB | CP | 0.07–2.1 × 106 CAR+T cells/kg | ORR, 88% (50 of 57) with 39 CRs, 3 VGPRs, 8 PRs | CRS: Gr1/2, 83% pts; Gr3/4, 7% pts CRES: Gr1, 1.8% pts | NCT03090659 [9] |
Multisite phase1/2,Nanjing Legend, China (LCAR-B38M)(RJ, JS, CZ) | 17 | 4-1BB | CP/Flu | 0.21–1.52 × 106 CAR+T cells/kg | ORR, 88.2% (15 of 17) with 13 sCRs, 2 VGPRs | Mild CRS, 10 pts; severe but manageable CRS, 6 pts; died of a very severe toxic reaction, 1 pt | ChiCTR-ONH-17012285 [24] |
Multisite phase 1, Poseida (P-BCMA-101) | 12 | 4-1BB | CP/Flu | 48–430 × 106 CAR+T cells | ORR, 89% (8 of 9 ) with 1 sCR,1 near CR, 1 VGPR, 5 PRs | CRS: Gr2, 1 pt | |
Multisite phase1/2, Juno (JCARH125) | 19 | 4-1BB | CP/Flu | 50/150 × 106 CAR+T cells | ORR, 100% (8 of 8) with 1 PR, 2 sCRs 1 CR, 2 VGPRs, 1 PR, 1 MR | CRS: Gr1/2, 75% pts, CRES, 38% pts | NCT03430011 [27] |
Multisite phase1, China (CT053) | 16 | 4-1BB | CP/Flu | 0.5/1.5/1.8 × 108 CAR+T cells | ORR, 100% (13 of 13) with 3 CRs, 6 VGPRs, 4 PRs | CRS: only 3 pts 1 each for Gr1-3 CRES: none | NCT03915184 [28] |
Celgene/MSKCC, phase 1 (MCARH171) | 11 | 4-1BB | CP/Flu | 72/137/475/818 × 106 CAR+T cells | ORR, 64% | CRS: Gr1/2, 40% pts; Gr3, 20% pts CRES: Gr2, 10% pts | NCT03070327 [29] |
Single site phase 1 (BRD015) | 28 | CD28 | CP/Flu | 5.4–25.0 × 106CAR+T cells/kg | ORR: BCMA strong expression group, 87%; BCMA weak expression group, 100% | CRS: Gr3, 14% pts | ChiCTR-OPC-16009113 [30] |
Single site phase 1 (CT103A) | 9 | 4-1BB | CP/Flu | 1/3/6 × 106 CAR+T cells/kg | ORR, 100%(9 of 9) with 4 CRs, 1 VGPR, 4 PRs | Mild CRS (first two dose levels) DLT: n = 1 (highest dose) | ChiCTR1800018137 [31] |
Single site phase 1 (CART-BCMA) | 25 | 4-1BB | CP or none | 1–50 × 107 CAR+T cells | ORR, 48%(12 of 25) with 1 sCR, 1 CR, 5 VGPRs, 5 PRs | CRS:Gr3/4, 32% pts CRES, 12% pts | NCT02546167 [33] |
Single site phase 1, HRAIN Biotechnology, China | 17 | 4-1BB | CP/Flu | 9 × 106 CAR+T cells/kg | ORR, 79%(11 of 14) with 3 sCRs, 4 CRs, 2 VGPRs, 2 MRs | Mild CRS | NCT03093168 [34] |
Multisite phase 1 in China | 4 | 4-1BB | CP/Flu | 5/10 × 106 CAR+T cells/kg | ORR, 100% (4 of 4) with 1 CR, 3 PRs | All CRS under Gr3 | NCT03661554 [35] |
Soochow University, China (BCMA- and CD19-targeted CAR-T combination trial) | 8 | OX40, CD28 | CP/Flu | 1 × 107/kg CD19-targeted CAR+T cells; 2.5–8.2 × 107/kg BCMA-targeted CAR+T cells | ORR, 80% (4 of 5) with 1 sCR, 1 VGPR, 2 PRs | Mild CRS | NCT03196414 [36] |
Soochow University, China (BCMA- and CD19- targeted CAR-T combination trial) | 9 | OX40, CD28 | Bu-CP + ASCT | 1 × 107/kg CD19-targeted CAR+T cells; 2.5-8.2 × 107/kg BCMA-targeted cells | ORR, 100% (9 of 9) with 3 CRs, 6 VGPRs | Mild CRS | NCT03455972 [37] |
Affiliated Hospital of Xuzhou Medical University, China (BCMA- and CD19-targeted CAR-T combination trial) | 21 | 4-1BB | CP/Flu | 1 × 106/kg both BCMA-and CD19-targeted CAR+T cells | ORR, 95% (20 of 21) with 9 sCRs, 3 CRs, 5 VGPRs, 3PRs | CRS: Gr1–2, 86% Gr3, 5% | ChiCTR-OIC-17011272 [42] |