Table 3.
BsAbs against BCMA in clinical development (Major clinical trials with published data).
| Drug | Target | Manufacturer | Therapeutic format and Mechanism of action | Dose | Dose schedule | Clinical outcome in Monotherapy | Reference |
|---|---|---|---|---|---|---|---|
| AMG420 (former BI 836909) | BCMA/CD3ϵ | Boehringer Ingelheim/Amgen | Bispecific single-chain variable fragment with hexahistidine tag antibody | 0.2–800 µg/day I.V. | 4 weeks of continuous I.V. infusion over a 6-weeks treatment cycle | RRMM, ORR 31%, | (152) |
| 70% at 400 μg/d (N = 7) | |||||||
| Pavurutamab (AMG701) | BCMA/CD3ϵ | Amgen | Bispecific single-chain variable fragment with hexahistidine tag antibody | Phase I dose-escalation study | 4 weeks of continuous I.V. infusion over a 6-weeks treatment cycle | RRMM, ORR 26%, | (153) |
| 83% at 18 mg dose (N = 6) | |||||||
| CC-93269 (former BCMA-TCB2/EM-901) | BCMA/CD3 (Dual BCMA binding site) | Celgene | Asymmetric two-arm IgG1-based human bispecific T-cell engaging antibody. In EM 901the heterodimeric Fc region has intact FCRn binding site | Phase I dose-escalation study | I.V. @ on days 1, 8, 15, and 22 of cycles 1 to 3, on days 1 and 15 of cycles 4 to 6, and on day 1 of cycle 7 | RRMM, ORR 43%, | (154) |
| 89% at 10 mg dose (N = 9) | |||||||
| TNB-383B | BCMA/CD3 (Dual BCMA binding site) | TeneoBio and Abbvie | T-cell engaging bispecific antibody, with unique selective activating anti-CD3 moiety, two heavy-chain-only anti-BCMA moieties for a 2:1 tumor associated antigen to CD3 stoichiometry, with an IgG4 silenced backbone to reduce nonspecific T-cell activation | Phase I dose-escalation study | 1–2 h I.V. infusions every 3 weeks | RRMM, ORR 47%, | (155) |
| 80% at 40–60 mg doses (N = 15) | |||||||
| Elranatamab (PF-06863135) | BCMA/CD3 | Pfizer Alexo Therapeutics Kodiak Sciences | Fully human IgG CD3 bispecific molecule, with IgG2A backbone | Phase I dose-escalation study, | Weekly subcutaneous | RRMM, ORR 53%, | (156) |
| 80–360 μg/kg (SC) | 80% at 215–1,000 µg/kg mg doses (N = 20) | ||||||
| 0.1–50 μg/kg (I.V.) | |||||||
| Teclistamab (JNJ-64007957) | BCMA/CD3 | Janssen Pharmaceutical Companies | DuoBody. Bispecific IgG1 molecule generated by controlled Fab-arm exchange of two separated mAbs | 80–3,000 μg/kg (SC) | Weekly I.V./SC | RRMM ORR 64%, | (157) |
| 0.3–720 μg/kg (I.V.) | |||||||
| REGN5458 | BCMA/CD3 | Regeneron and Sanofi | BCMA x CD3 bispecific antibody | Phase I dose-escalation study | Weekly I.V. ×16, then every 2 weeks | RRMM ORR 39%, | (158) |
| 3–96 mg | 63% at 96 mg dose (N = 8) |