Table 1.
Preliminary Clinical Data of Bispecific Antibodies in Multiple Myeloma.
| Drug | Targets | Company | Grade 3-4 TEAE | CRS | Response Rate | Survival (e.g. PFS, DOR, OS) |
|---|---|---|---|---|---|---|
| Elranatamab (PF-06863135) (65) |
anti-CD3/BCMA | Pfizer | neutropenia 60%, anemia 38%, lymphopenia 64%, thrombocytopenia 31% | 83% | At RP2D- ORR: 83%; sCR: 83% | median DOR not reached |
| REGN5458 (66) | anti-CD3/BCMA | Regeneron | anemia 9%, lymphopenia 7%, infections 20% | 38% | At all doses-ORR: 36%; CR: 31% | 43.8% of responders DOR > 4 m; 18.8% responders DOR > 8 m |
| Teclistamab (67) | anti-CD3/BCMA | Janssen | neutropenia 45%, anemia 27%, thrombocytopenia 18%, fatigue 2% | At RP2D- 67% | At RP2D- ORR: 65%; ≥VGPR: 60%; ≥CR: 40% | median DOR not reached; 6 m DOR: 90% (95% CI 63-97) |
| AMG 701 (68) | anti-CD3/BCMA | Amgen | CRS 7%, atrial fibrillation 1%, acidosis 1%, thrombocytopenia 1% | 61% | At 3-12mg- ORR: 36%; sCR: 4% | median DOR: 3.8 m (ongoing in 14/17 pts); maximum DOR: 23 m |
| TNB-383B (69) | anti-CD3/BCMA | TeneBio/ Abbvie |
CRS 3% | 52% | At ≥40 mg- ORR: 64%; ≥VGPR: 43%; CR: 16% | At ≥40 mg- ORR: 64%; ≥VGPR: 43%; CR: 16% |
| AMG420 (70) | anti-CD3/BCMA | Amgen | CRS 2%, polyneuropathy 5%, edema 2% | 38% | At all doses- ORR: 31%; ≥CR: 21% | median DOR > 8.4 m |
| CC-93269 (71) | anti-CD3/BCMA | Celgene | neutropenia 43%, anemia 37%, infections 30%, thrombocytopenia 17% | 77% | At all doses- ORR: 43%; ≥CR: 17% | DOR: 5.3-40.6 m |
| Talquetamab (72) | anti-CD3/GPRC5D | Janssen | 405 µg/kg weekly: CRS 3%, neutropenia 60%, infections 3% 800ug/kg biweekly: neutropenia 35%, infections 4% |
405 µg/kg weekly: 73% 800ug/kg biweekly: 78% |
At 405 µg/kg weekly- ORR: 70%; ≥VGPR: 57% At 800 µg/kg biweekly dose- ORR: 71%; ≥VGPR rate: 53% |
6 m DOR for pts given 405ug/kg dose: 67% [95% CI: 41-84]; median DOR not reached |
| Cevostamab (BFCR4350A) (73) |
anti-CD3/FcRH5 | Genentech | CRS 1%, anemia 22%, neutropenia 16%, infections 19% | 80% | At 160mg dose- ORR: 55% At 90mg dose- ORR: 37% | median DOR: estimated 15.6 m (95% CI: 6.4-21.6 m) |
TEAE, treatment-related adverse events; CRS, cytokine release syndrome; RP2D, recommended phase 2 dose; ORR, overall response rate; sCR, stringent complete response; CR, complete response; VGPR, very good partial response; PFS, progression-free survival; DOR, duration of response; OS, overall survival; m, month; yr, year; pts, patients.