Main reported clinical trials of BCMA-directed CAR T cells in RRMM
| . | BB21217 CRB-402 (n = 72) . | Orva-cel EVOLVE (n = 62) . | CT053 LUMMICAR (n = 18) . | CT103A FUMANBA-1 (n = 79) . | C-CAR088 (n = 23) . | P-BCMA-101 PRIME (n = 53) . | ALLO-715 UNIVERSAL (n = 43) . | ARI-002h (n = 30) . |
|---|---|---|---|---|---|---|---|---|
| Phase | 1 | 1 | 1b/2 | 1/2 | 1 | 1/2 | 1 | 1 |
| Follow-up, median (range) | 23 (9-46) | 9.5 mo | 6 mo (2-11) | 25.3 mo (4.1-36.7) | 6.2 mo (0.7-16.1) | NA | 4 mo | 13 mo (7-13) |
| Target/costimulation | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB |
| scFv | Mouse | Mouse | Human | Human | Human | Mouse | Human | Human |
| Specificity | Autologous | Autologous | Autologous | Autologous | Autologous | Autologous | Allogeneic | Autologous |
| CAR T-cell dose | 150-450 M | 300-600 M | 1.5-3.0 × 108 cells | 1.0 × 106/kg | 1.0-6.0 × 106/kg | 51-1178 × 106 | 40-480 × 106 | 3 × 106/kg |
| Population | ||||||||
| Age, median (range) | 62 (33-76) | 61 (33-77) | 62 (36-78) | 56 (39-70) | 60 (45-74) | 60 (42-74) | 64 (46-77) | 61 (36-74) |
| Prior lines, median (range) | 6 (3-17) | 6 (3-18) | 5 (3-11) | 5 (3-13) | 4 (2-12) | 8 (2-18) | 5 (3-11) | 4 (2-10) |
| Triple-class refractory, n (%) | 50 (69) | 58 (94) | 85% | 13 (16.5) | NR | 60% | NR | 61% |
| Penta-refractory, n (%) | NR | 30 (48) | 50% | NR | NR | NR | 42% | NR |
| Efficacy | At 320 × 106 | |||||||
| ORR, n (%) | 69% | 92% | 94% | 75 (94.9) | 22 (95.7) | 50%-75% | 71% | 100% |
| CR, n (%) | 36% | 36% | 27.8% | 58.2% | 43.5% | NR | 25% | 60% |
| PFS (mo), median (95% CI) | 12.8 mo (7.3-18.6) | 9.3 mo (300 M) | NR | 25.3 mo (3.0-NE) | 6 mo PFS: 65.1% | NR | NR | 15.8 mo (12.9-NE) |
| CRS | ||||||||
| All grade, n (%) | 54 (75) | 55 (89) | 15/18 (83.3) | 72 (92.4) | 21 (91.3) | 17% | 24 (56) | 87% |
| Grade 3-4, n (%) | 3 (2 grade 5) | 2 (3) | 0 (0) | 2 (2.5) | 1 (4.3) | 0% | 1 (2) | 0 (0) |
| Onset (d), median (range) | 2 d (1-20) | 2 (1-4) | 2 (DL0) & 1 (DL1) | 6 (1-12) | 6 (1-11) | NR | NR | NR |
| Duration (d), median (range) | 4 d | 4 (1-10) | 4 (DL0) & 3 (DL1) | 5 (1-30) | 5 (2-9) | NR | NR | 4 (1-12) |
| Tocilizumab/steroids %/% | 53/17 | 76/52 | ≈30/20 | 20/34.7 | 26/9 | 7/6 | 23/14 | 76/12 |
| ICANS | ||||||||
| All grade, n (%) | 11 (15) | 8 (13) | 2 (DL0) & 1 (DL1) | 1 (1.3) | 1 (4.3) | 4% | 6 (14) | 0 |
| Grade 3-4, n (%) | 3 (4) | 2 (3) | 1 patient | 0 | 0 (0) | 4% | 0 (0) | 0 |
| Onset (d), median (range) | 7 d (2-24) | 4 (1-6) | NR | 10 | 8 | NR | NR | — |
| Duration (d), median (range) | 2 d | 4 (1-10) | NR | 1 | 1 | NR | NR | — |
| Status | Not further developed | Not further developed | Ongoing | Ongoing | Ongoing | Not further developed | Ongoing | Ongoing |
| Reference | Raje et al27 | Mailankody et al.37 | Chen et al.38 | Chunrui et al.39 | Gan An, et al.40 | Costello et al.41 | Mailankody et al.42 | de Larrea et al24 |
| Identification | NCT03274219 | NCT03430011 | NCT03915184 | NCT05066646 | NCT05066646 | NCT03288493 | NCT04093596 | NCT04309981 |
| . | BB21217 CRB-402 (n = 72) . | Orva-cel EVOLVE (n = 62) . | CT053 LUMMICAR (n = 18) . | CT103A FUMANBA-1 (n = 79) . | C-CAR088 (n = 23) . | P-BCMA-101 PRIME (n = 53) . | ALLO-715 UNIVERSAL (n = 43) . | ARI-002h (n = 30) . |
|---|---|---|---|---|---|---|---|---|
| Phase | 1 | 1 | 1b/2 | 1/2 | 1 | 1/2 | 1 | 1 |
| Follow-up, median (range) | 23 (9-46) | 9.5 mo | 6 mo (2-11) | 25.3 mo (4.1-36.7) | 6.2 mo (0.7-16.1) | NA | 4 mo | 13 mo (7-13) |
| Target/costimulation | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB | BCMA/4-1BB |
| scFv | Mouse | Mouse | Human | Human | Human | Mouse | Human | Human |
| Specificity | Autologous | Autologous | Autologous | Autologous | Autologous | Autologous | Allogeneic | Autologous |
| CAR T-cell dose | 150-450 M | 300-600 M | 1.5-3.0 × 108 cells | 1.0 × 106/kg | 1.0-6.0 × 106/kg | 51-1178 × 106 | 40-480 × 106 | 3 × 106/kg |
| Population | ||||||||
| Age, median (range) | 62 (33-76) | 61 (33-77) | 62 (36-78) | 56 (39-70) | 60 (45-74) | 60 (42-74) | 64 (46-77) | 61 (36-74) |
| Prior lines, median (range) | 6 (3-17) | 6 (3-18) | 5 (3-11) | 5 (3-13) | 4 (2-12) | 8 (2-18) | 5 (3-11) | 4 (2-10) |
| Triple-class refractory, n (%) | 50 (69) | 58 (94) | 85% | 13 (16.5) | NR | 60% | NR | 61% |
| Penta-refractory, n (%) | NR | 30 (48) | 50% | NR | NR | NR | 42% | NR |
| Efficacy | At 320 × 106 | |||||||
| ORR, n (%) | 69% | 92% | 94% | 75 (94.9) | 22 (95.7) | 50%-75% | 71% | 100% |
| CR, n (%) | 36% | 36% | 27.8% | 58.2% | 43.5% | NR | 25% | 60% |
| PFS (mo), median (95% CI) | 12.8 mo (7.3-18.6) | 9.3 mo (300 M) | NR | 25.3 mo (3.0-NE) | 6 mo PFS: 65.1% | NR | NR | 15.8 mo (12.9-NE) |
| CRS | ||||||||
| All grade, n (%) | 54 (75) | 55 (89) | 15/18 (83.3) | 72 (92.4) | 21 (91.3) | 17% | 24 (56) | 87% |
| Grade 3-4, n (%) | 3 (2 grade 5) | 2 (3) | 0 (0) | 2 (2.5) | 1 (4.3) | 0% | 1 (2) | 0 (0) |
| Onset (d), median (range) | 2 d (1-20) | 2 (1-4) | 2 (DL0) & 1 (DL1) | 6 (1-12) | 6 (1-11) | NR | NR | NR |
| Duration (d), median (range) | 4 d | 4 (1-10) | 4 (DL0) & 3 (DL1) | 5 (1-30) | 5 (2-9) | NR | NR | 4 (1-12) |
| Tocilizumab/steroids %/% | 53/17 | 76/52 | ≈30/20 | 20/34.7 | 26/9 | 7/6 | 23/14 | 76/12 |
| ICANS | ||||||||
| All grade, n (%) | 11 (15) | 8 (13) | 2 (DL0) & 1 (DL1) | 1 (1.3) | 1 (4.3) | 4% | 6 (14) | 0 |
| Grade 3-4, n (%) | 3 (4) | 2 (3) | 1 patient | 0 | 0 (0) | 4% | 0 (0) | 0 |
| Onset (d), median (range) | 7 d (2-24) | 4 (1-6) | NR | 10 | 8 | NR | NR | — |
| Duration (d), median (range) | 2 d | 4 (1-10) | NR | 1 | 1 | NR | NR | — |
| Status | Not further developed | Not further developed | Ongoing | Ongoing | Ongoing | Not further developed | Ongoing | Ongoing |
| Reference | Raje et al27 | Mailankody et al.37 | Chen et al.38 | Chunrui et al.39 | Gan An, et al.40 | Costello et al.41 | Mailankody et al.42 | de Larrea et al24 |
| Identification | NCT03274219 | NCT03430011 | NCT03915184 | NCT05066646 | NCT05066646 | NCT03288493 | NCT04093596 | NCT04309981 |
Data of safety and efficacy are shown.
NR, not reached.