Summary of bispecific T-cell antibodies for MM
| Name . | Target . | Antibody construct . | Triple-class refractory (median LoT) . | Trial phase . | Schedule . | Preliminary response/activity . | Safety . | Current status (ClinicalTrials.gov) . |
|---|---|---|---|---|---|---|---|---|
| AMG 42038 | BCMA-CD3 | BiTE® | N/A (29% prior anti-CD38, median 5 LoT) | Phase 1 | Continuous infusion for 4 wk (out of 6) | ORR = 31% ORR MTD = 70% | 38% CRS (6.25% ≥ gr 3) 5% ≥ gr 3 polyneuropathy 24% ≥ gr 3 infection | Active, not recruiting NCT03836053 |
| AMG 70139 | BCMA-CD3 | HLE-BiTE® | 68% (median 6 LoT) | Phase 1/2 | Weekly IV | ORR = 36% ORR = 83% at 9 mg | 75% CRS (10.5% ≥ gr 3) 8% neurotoxicity (gr 1-2) 13% ≥ gr 3 infection | Recruiting NCT03287908 |
| Elranatamab41 | BCMA-CD3 | Humanized IgG2a Fc | 91% (median 6 LoT; 22% prior anti-BCMA) | Phase 1 | Weekly or every 2 wk Sc | ORR = 64% for doses ≥215 µg/kg | 67% CRS (gr 1-2) | MagnetisMM-1 Recruiting NCT03269136 |
| REGN545842 | BCMA-CD3 | Fc Fab arms | 97.1% (median 5 LoT) | Phase 1/2 | Weekly IV | ORR = 73.3% at 96-200-mg doses | 38.2% CRS (gr 1-2) 4% neurotoxicity (gr 1-2) 23% pneumonia (11% ≥ gr 3) | Recruiting NCT03761108 |
| Teclistamab40 | BCMA-CD3 | Humanized IgG4 Fc | 77.8% (median 5 LoT; prior anti-BCMA not permitted) | Phase 1/2 | Weekly Sc | ORR = 63% | 72.1% CRS (gr 3, 0.6%; no gr 4) 14.5% neurotoxicity (1 gr 4 event) 44.8% ≥ gr 3 infection | MajestTEC-1 Recruiting NCT03145181 |
| CC-9326944 | BCMA-CD3 | Asymmetric 2-arm IgG | 66.7% (median 6 LoT) | Phase 1 | Weekly IV | ORR = 83.3% in 10 pts with doses ≥6 mg | 89.5% CRS (1 gr 5 event) 26.3% infection | Recruiting NCT03486067 |
| TNB-383B44 | BCMA-CD3 | IgG4 Fc CD3 activating T effector cells | 62% (median 5 LoT) | Phase 1 | Q21d IV | ORR = 79% at doses ≥40 mg | 52% CRS (3% ≥ gr 3 at RP2D) 28% infection | Recruiting NCT03933735 |
| Cevostamab45 | FcRH5-CD3 | Humanized IgG1 Fc | 85% (median 6 LoT; 33.5% prior anti-BCMA) | Phase 1 | Q21d IV | ORR = 54.5% at 160-mg-dose level | 80.7% CRS (1.3% ≥ gr 3) 18.8% ≥ gr 3 infection 14.3% neurotoxicity (0.3% ≥ gr 3) | Recruiting NCT03275103 |
| Talquetamab46 | GPRC5D-CD3 | Humanized IgG4 Fc | Weekly: 77% (median 6 LoT; 30% prior anti-BCMA) Biweekly: 65% (median 5 LoT; 17% prior anti-BCMA) | Phase 1/2 | Weekly or biweekly Sc | Weekly: ORR = 70% Biweekly: ORR = 71% | Weekly: 73% CRS (1 gr 3) Biweekly: 78% CRS (gr 1-2) | MonumenTal-1 Recruiting NCT03399799 |
| Name . | Target . | Antibody construct . | Triple-class refractory (median LoT) . | Trial phase . | Schedule . | Preliminary response/activity . | Safety . | Current status (ClinicalTrials.gov) . |
|---|---|---|---|---|---|---|---|---|
| AMG 42038 | BCMA-CD3 | BiTE® | N/A (29% prior anti-CD38, median 5 LoT) | Phase 1 | Continuous infusion for 4 wk (out of 6) | ORR = 31% ORR MTD = 70% | 38% CRS (6.25% ≥ gr 3) 5% ≥ gr 3 polyneuropathy 24% ≥ gr 3 infection | Active, not recruiting NCT03836053 |
| AMG 70139 | BCMA-CD3 | HLE-BiTE® | 68% (median 6 LoT) | Phase 1/2 | Weekly IV | ORR = 36% ORR = 83% at 9 mg | 75% CRS (10.5% ≥ gr 3) 8% neurotoxicity (gr 1-2) 13% ≥ gr 3 infection | Recruiting NCT03287908 |
| Elranatamab41 | BCMA-CD3 | Humanized IgG2a Fc | 91% (median 6 LoT; 22% prior anti-BCMA) | Phase 1 | Weekly or every 2 wk Sc | ORR = 64% for doses ≥215 µg/kg | 67% CRS (gr 1-2) | MagnetisMM-1 Recruiting NCT03269136 |
| REGN545842 | BCMA-CD3 | Fc Fab arms | 97.1% (median 5 LoT) | Phase 1/2 | Weekly IV | ORR = 73.3% at 96-200-mg doses | 38.2% CRS (gr 1-2) 4% neurotoxicity (gr 1-2) 23% pneumonia (11% ≥ gr 3) | Recruiting NCT03761108 |
| Teclistamab40 | BCMA-CD3 | Humanized IgG4 Fc | 77.8% (median 5 LoT; prior anti-BCMA not permitted) | Phase 1/2 | Weekly Sc | ORR = 63% | 72.1% CRS (gr 3, 0.6%; no gr 4) 14.5% neurotoxicity (1 gr 4 event) 44.8% ≥ gr 3 infection | MajestTEC-1 Recruiting NCT03145181 |
| CC-9326944 | BCMA-CD3 | Asymmetric 2-arm IgG | 66.7% (median 6 LoT) | Phase 1 | Weekly IV | ORR = 83.3% in 10 pts with doses ≥6 mg | 89.5% CRS (1 gr 5 event) 26.3% infection | Recruiting NCT03486067 |
| TNB-383B44 | BCMA-CD3 | IgG4 Fc CD3 activating T effector cells | 62% (median 5 LoT) | Phase 1 | Q21d IV | ORR = 79% at doses ≥40 mg | 52% CRS (3% ≥ gr 3 at RP2D) 28% infection | Recruiting NCT03933735 |
| Cevostamab45 | FcRH5-CD3 | Humanized IgG1 Fc | 85% (median 6 LoT; 33.5% prior anti-BCMA) | Phase 1 | Q21d IV | ORR = 54.5% at 160-mg-dose level | 80.7% CRS (1.3% ≥ gr 3) 18.8% ≥ gr 3 infection 14.3% neurotoxicity (0.3% ≥ gr 3) | Recruiting NCT03275103 |
| Talquetamab46 | GPRC5D-CD3 | Humanized IgG4 Fc | Weekly: 77% (median 6 LoT; 30% prior anti-BCMA) Biweekly: 65% (median 5 LoT; 17% prior anti-BCMA) | Phase 1/2 | Weekly or biweekly Sc | Weekly: ORR = 70% Biweekly: ORR = 71% | Weekly: 73% CRS (1 gr 3) Biweekly: 78% CRS (gr 1-2) | MonumenTal-1 Recruiting NCT03399799 |
Note: This list is not exhaustive for all bispecific T-cell antibodies developed for MM.
Fab, fragment antigen-binding; gr, grade; HLE, half-life extended; IV, intravenous; LoT, lines of therapy; pts, patients; Q21d, every 21 days; RP2D, recommended phase 2 dose; Sc, subcutaneous; wk, week.