Safety and efficacy of BispAbs
| . | CC-9326938 n = 30 . | AMG70139 N = 75 . | Teclistamab39 n = 159 . | Elranatamab40 n = 50 . | RENG545841 n = 68 . | Tnb-383B42 n = 103 . | Talquetamab43 n = 95 . | Cevostamab44 n = 160 . |
|---|---|---|---|---|---|---|---|---|
| Target | BCMA | BCMA | BCMA | BCMA | BCMA | BCMA | GPRC5D | FcRH5 |
| Phase | 1 | 1 | 1/2 | 1 | 1/2 | 1 | 1 | 1 |
| Administration | IV* | IV weekly | SC weekly | SC Q2W | IV weekly, then Q2W | IV Q3W | SC weekly or Q2W | IV Q3W |
| Median number of prior regimens | 5 (3-13) | 6 (1-25) | 5 (2-15) | 6 | 5 (2-17) | 5 (1-15) | NR | 6 (2-18) |
| Median age, y | 64 (42-78) | 63 | 64 (33-84) | 64 (32-86) | 64 (41-81) | 67 (35-88) | 61 (46-84) | 64 (33-82) |
| Triple refractory (%) | NR | 68 | 77 | 98 | 100 | 62 | 81 | 85 |
| RP2D | Not reached | Not reported | 1.5 mg/kg weekly | 1 mg/kg | NR | 60 mg Q3W | 405 μg/kg weekly or 800 μg/kg Q2W | NR |
| CRS, grade ≥3 (%) | 77, 4 | 61, 7 | 67, 1 | 83, 0 | 38, 0 | 52, 3 | 73, 3 at 405 μg/kg weekly 78, 0 at 800 μg/kg Q2W | 80, 1 |
| Median duration of CRS (d) | NR | 2 | 2 (1-9) | 2 | NR | NR | NR | 2 |
| Median time to onset of CRS (d) | NR | NR | 2 (1-6) | NR | NR | 1 | NR | 1 |
| Neurotoxicity, grade ≥3 (%) | NR | 8, 0 | 2.5, 0 | NR | NR, 0 | NR | NR | 13.1, 3.8 |
| Neutropenia, grade ≥3 (%) | NR, 43 | 23, NR | 53, 45 | 64, 60 | 16, 13 | 17, NR | 67, 60 at 405 μg/kg weekly 44, 35 at 800 μg/kg Q2W | 15, 13.8 |
| Anemia, grade ≥3 (%) | NR, 37 | 43, NR | 41, 27 | 55, 38 | NR | 9, NR | NR | 31.9, 21.9 |
| Thrombocytopenia, grade ≥3 (%) | NR, 17 | 20, NR | 33, 18 | 52, 31 | NR | 14, NR | NR | NR |
| Infections, grade ≥3 (%) | NR, 30 | NR, 17 | 45, 22.537 | NR | NR | 28, NR | 37, NR at 405 μg/kg weekly 13, NR at 800 μg/kg Q2W | 42.5, 18.8 |
| ORR across all dose levels (%) | 43 | 23.6 | NR | NR | NR | NR | NR | NR |
| ORR at RP2D or efficacious dose range (%) | 89 (9/10 at 10 mg) | 83 (5/6 at 9 mg) | 65 | 70 | 73.3 at 96 mg + 200 mg dose levels | 64 for cohorts ≥ 40 mg | 70 at 405 μg/kg weekly 71 at 800 μg/kg Q2W | 36.7 at 90 mg 54.5 at 160 mg |
| Median time to response (d) | 29 | 29 | 29 | 22 | NR | NR | NR | 29 |
| DOR | 5.3 to 40.6 wk | 3.8 mo (1.9, 7.4) | 6 mo: 90% | 95% CI at 6 mo: 92.3% (56.7-98.9) | DOR ≥ 8 mo: 92.1% | NR | 6 mo: 67% at 405 μg/kg weekly | Median: 15.6 mo (95% CI: 6.4-21.6) |
| . | CC-9326938 n = 30 . | AMG70139 N = 75 . | Teclistamab39 n = 159 . | Elranatamab40 n = 50 . | RENG545841 n = 68 . | Tnb-383B42 n = 103 . | Talquetamab43 n = 95 . | Cevostamab44 n = 160 . |
|---|---|---|---|---|---|---|---|---|
| Target | BCMA | BCMA | BCMA | BCMA | BCMA | BCMA | GPRC5D | FcRH5 |
| Phase | 1 | 1 | 1/2 | 1 | 1/2 | 1 | 1 | 1 |
| Administration | IV* | IV weekly | SC weekly | SC Q2W | IV weekly, then Q2W | IV Q3W | SC weekly or Q2W | IV Q3W |
| Median number of prior regimens | 5 (3-13) | 6 (1-25) | 5 (2-15) | 6 | 5 (2-17) | 5 (1-15) | NR | 6 (2-18) |
| Median age, y | 64 (42-78) | 63 | 64 (33-84) | 64 (32-86) | 64 (41-81) | 67 (35-88) | 61 (46-84) | 64 (33-82) |
| Triple refractory (%) | NR | 68 | 77 | 98 | 100 | 62 | 81 | 85 |
| RP2D | Not reached | Not reported | 1.5 mg/kg weekly | 1 mg/kg | NR | 60 mg Q3W | 405 μg/kg weekly or 800 μg/kg Q2W | NR |
| CRS, grade ≥3 (%) | 77, 4 | 61, 7 | 67, 1 | 83, 0 | 38, 0 | 52, 3 | 73, 3 at 405 μg/kg weekly 78, 0 at 800 μg/kg Q2W | 80, 1 |
| Median duration of CRS (d) | NR | 2 | 2 (1-9) | 2 | NR | NR | NR | 2 |
| Median time to onset of CRS (d) | NR | NR | 2 (1-6) | NR | NR | 1 | NR | 1 |
| Neurotoxicity, grade ≥3 (%) | NR | 8, 0 | 2.5, 0 | NR | NR, 0 | NR | NR | 13.1, 3.8 |
| Neutropenia, grade ≥3 (%) | NR, 43 | 23, NR | 53, 45 | 64, 60 | 16, 13 | 17, NR | 67, 60 at 405 μg/kg weekly 44, 35 at 800 μg/kg Q2W | 15, 13.8 |
| Anemia, grade ≥3 (%) | NR, 37 | 43, NR | 41, 27 | 55, 38 | NR | 9, NR | NR | 31.9, 21.9 |
| Thrombocytopenia, grade ≥3 (%) | NR, 17 | 20, NR | 33, 18 | 52, 31 | NR | 14, NR | NR | NR |
| Infections, grade ≥3 (%) | NR, 30 | NR, 17 | 45, 22.537 | NR | NR | 28, NR | 37, NR at 405 μg/kg weekly 13, NR at 800 μg/kg Q2W | 42.5, 18.8 |
| ORR across all dose levels (%) | 43 | 23.6 | NR | NR | NR | NR | NR | NR |
| ORR at RP2D or efficacious dose range (%) | 89 (9/10 at 10 mg) | 83 (5/6 at 9 mg) | 65 | 70 | 73.3 at 96 mg + 200 mg dose levels | 64 for cohorts ≥ 40 mg | 70 at 405 μg/kg weekly 71 at 800 μg/kg Q2W | 36.7 at 90 mg 54.5 at 160 mg |
| Median time to response (d) | 29 | 29 | 29 | 22 | NR | NR | NR | 29 |
| DOR | 5.3 to 40.6 wk | 3.8 mo (1.9, 7.4) | 6 mo: 90% | 95% CI at 6 mo: 92.3% (56.7-98.9) | DOR ≥ 8 mo: 92.1% | NR | 6 mo: 67% at 405 μg/kg weekly | Median: 15.6 mo (95% CI: 6.4-21.6) |
DOR, duration of response; NR, not reported; ORR, overall response rate; Q2W, every 2 weeks; Q3W, every 3 weeks; RP2D, recommended phase 2 dose; SC, subcutaneous.
On days D1, 8, 15, and 22 for cycles (C) 1-3; D1 and 15 for C4-6; and on D1 for C7 and beyond, all in 28-day cycles for up to 2 years.