Novel TAA and bispecific BCMA-targeted CAR T-cell therapies and their respective clinical trials
| Target . | GPRC5D . | GPRC5D . | GPRC5D . | CD138 . | BCMA/CD38 bispecific . | BCMA/CD38 bispecific . | BCMA/CS1 bispecific . |
|---|---|---|---|---|---|---|---|
| Drug (study) | MCARH10918 | BMS-98639319 (CC-95266) | OriCAR-01720 (POLARIS NCT05016778) | CART-13821 (NCT01886976) | BM38 CAR22 | BCMA-CD3823 | CS1-BCMA bispecific CAR24 (NCT04662099) |
| Phase | 1 | 1 | 1 | 1/2 | 1 | 1 | 1 |
| Median age (range), y | 60 (38-76) | — | 65 | 57 (48-68) | 59 (49-72) | 58.5 (48-78) | — |
| Med follow-up (range), mo | 10.1 | 5.9 (0.0-24/0) | 7.8 (6-10) | — | 9 | 11.5 | 8.2 |
| Median prior LOTs (range) | 6 (4-14) | — | 6 (3-17) | 8 (5-18) | 4 (2-9) | 3 (2-3) | 4 (2-8) |
| Previous BCMA therapies, % | 59 | 46 | 50 | — | 0 | 0 | 13 |
| Cohort size, n | 17 | 70 | 10 | 5 | 23 | 16 | 16 |
| Efficacy, % | |||||||
| ORR | 71 | 86 | 100 | 0 | 87 | 87.5 | 81 |
| CR/sCR | 35 | 38 | 60 | 0 | 52 | 81.2 | 38 |
| PFS | — | — | — | — | — | 1-y PFS 68.8% | mPFS: 9 mo |
| OS | — | — | — | — | — | 1-y OS: 75% | mOS: NR |
| DOR | mDOR: 7.8 mo | — | — | — | — | — | mDOR: NR |
| Safety, % | |||||||
| CRS all grades/G3+ | 88/6 | 84/6 | 100/0 | 80/0 | 87/17 | 75/31.3 | 38/6 |
| ICANS all grades/G3+ | 6/6 | 11/4 | 0/0 | — | 0/0 | -/- | 0/0 |
| Neutropenia all grades/G3+ | 100/100 | -/69 | 100/100 | — | 96/87 | -/- | 100/94 |
| Anemia all grades/G3+ | 88/41 | -/31 | -/70 | — | 43/13 | -/38 | 25/13 |
| Thrombocytopenia all grades/G3+ | 88/65 | -/30 | -/90 | — | 61/47 | -/25 | 63/31 |
| Other/other G3+ | Infection 18/12 Nail changes 65/0 Dysgeusia 12/0 | Skin TEAE 24/0 Nail changes 16/0 Dysgeusia 3/0 | Lung infection 4/4 | Leukopenia -/94 Infection 38/- Myalgia 50/- Migratory arthralgia 31/- |
| Target . | GPRC5D . | GPRC5D . | GPRC5D . | CD138 . | BCMA/CD38 bispecific . | BCMA/CD38 bispecific . | BCMA/CS1 bispecific . |
|---|---|---|---|---|---|---|---|
| Drug (study) | MCARH10918 | BMS-98639319 (CC-95266) | OriCAR-01720 (POLARIS NCT05016778) | CART-13821 (NCT01886976) | BM38 CAR22 | BCMA-CD3823 | CS1-BCMA bispecific CAR24 (NCT04662099) |
| Phase | 1 | 1 | 1 | 1/2 | 1 | 1 | 1 |
| Median age (range), y | 60 (38-76) | — | 65 | 57 (48-68) | 59 (49-72) | 58.5 (48-78) | — |
| Med follow-up (range), mo | 10.1 | 5.9 (0.0-24/0) | 7.8 (6-10) | — | 9 | 11.5 | 8.2 |
| Median prior LOTs (range) | 6 (4-14) | — | 6 (3-17) | 8 (5-18) | 4 (2-9) | 3 (2-3) | 4 (2-8) |
| Previous BCMA therapies, % | 59 | 46 | 50 | — | 0 | 0 | 13 |
| Cohort size, n | 17 | 70 | 10 | 5 | 23 | 16 | 16 |
| Efficacy, % | |||||||
| ORR | 71 | 86 | 100 | 0 | 87 | 87.5 | 81 |
| CR/sCR | 35 | 38 | 60 | 0 | 52 | 81.2 | 38 |
| PFS | — | — | — | — | — | 1-y PFS 68.8% | mPFS: 9 mo |
| OS | — | — | — | — | — | 1-y OS: 75% | mOS: NR |
| DOR | mDOR: 7.8 mo | — | — | — | — | — | mDOR: NR |
| Safety, % | |||||||
| CRS all grades/G3+ | 88/6 | 84/6 | 100/0 | 80/0 | 87/17 | 75/31.3 | 38/6 |
| ICANS all grades/G3+ | 6/6 | 11/4 | 0/0 | — | 0/0 | -/- | 0/0 |
| Neutropenia all grades/G3+ | 100/100 | -/69 | 100/100 | — | 96/87 | -/- | 100/94 |
| Anemia all grades/G3+ | 88/41 | -/31 | -/70 | — | 43/13 | -/38 | 25/13 |
| Thrombocytopenia all grades/G3+ | 88/65 | -/30 | -/90 | — | 61/47 | -/25 | 63/31 |
| Other/other G3+ | Infection 18/12 Nail changes 65/0 Dysgeusia 12/0 | Skin TEAE 24/0 Nail changes 16/0 Dysgeusia 3/0 | Lung infection 4/4 | Leukopenia -/94 Infection 38/- Myalgia 50/- Migratory arthralgia 31/- |
CR, complete remission; DOR, duration of response; G3, grade 3; mDOR, median duration of response; NR, not reached; Q2W, once every 2 weeks; QW, once weekly; sCR, stringent complete remission; TEAE, treatment-emergent AE.