Table 1.
An overview of clinical trials assessing T cell-redirecting bispecific antibodies in heavily pre-treated multiple myeloma patients.
| Targets | Drug Name | Design | Trial Type (Phase) | Enrolled Patients | Overall Response Rate | Minimal Residual Disease | Cytokine Release Syndrome | Clinical Trial Identifier/Reference |
|---|---|---|---|---|---|---|---|---|
| BCMA x CD3 | Pacanalotamab (AMG 420) | BiTE | 1 | 42 | 31% (13 of 42 patients, IV); 70% (7 of 10 patients) at the MTD (400 µg/day) | 71% (5 of 7 patients) at the MTD | 38% (16 of 42 patients): Grade 1 = 28%; Grade 2 = 5%; Grade 3 = 2% | NCT02514239 [34] |
| BCMA x CD3 | Pavurutamab (AMG 701) | Half-life extended BiTE (scFvs plus Fc domain) | 1 | 85 | 26% (21 of 82 patients, IV); 83% (5 of 6 patients) at the most recent evaluable cohort | 85% (6 of 7 patients) across all cohorts | 65% (55 of 85 patients): Grade 1 = 27%; Grade 2 = 28%; Grade 3 = 9% | NCT03287908 [36] |
| BCMA x CD3 | Elranatamab (PF-06863135) | IgG2a Fc region | 1 | 30 (SC administration) | 70% at SC doses ≥215 µg/kg (14 of 20 patients); 83% (5 of 6 patients) at the RP2D (1000 µg/kg) | 100% (3 of 3 patients) across all cohorts | 73.3%: Grade 1 = 57%; Grade 2 = 17% (no events >grade 2) | NCT03269136 [37] |
| BCMA x CD3 | Teclistamab (JNJ-64007957) | IgG4 Fc region | 1 | 157 total 40 at the RP2D |
65% (26 of 40 patients) at the RP2D (SC 1500 µg/kg) | 100% (6 of 6 evaluable patients treated at the RP2D); 69% (18 of 26 patients) across both IV and SC cohorts | 70% (28 of 40 patients) at the RP2D: Grade 1 = 45%; Grade 2 = 25% (no events >grade 2) | NCT03145181 [38,39] |
| BCMA x CD3 | REGN5458 | VelociBiTM Fc region | 1 | 49 | 39% (19 of 49 patients, IV); 63% in dose-level 6 (8 patients) | 57% (4 of 7 patients) across all cohorts | 39% (19 of 49 patients): Grade 1 = 33%; Grade 2 = 6% (no events >grade 2) | NCT03761108 [40] |
| BCMA x CD3 | REGN5459 | VelociBiTM Fc region | 1 | N/A | N/A | N/A | N/A | NCT04083534 |
| BCMA x CD3 | TNB-383B | IgG4 Fc region | 1 | 58 | 46.5% (27 of 58 patients, IV); 80% (12 of 15 patients) at IV doses ≥ 40 mg | 75% (3 of 4 patients) across all cohorts | 80% (12 of 15 patients treated at IV doses ≥ 40 mg): Grade 1 = 46.7%; Grade 2 = 33.3% (no events >grade 2) | NCT03933735 [41] |
| BCMA x CD3 | CC-93269 | IgG1-based Fc region | 1 | 30 | 43% (13 of 30 patients, IV); 89% (8 of 9 patients) at highest dose of 10 mg | 92% (12 of 13 patients) across all cohorts | 77% (23 of 30 patients): Grade 1 = 50%; Grade 2 = 23%; grade ≥3 = 3% | NCT03486067 [42] |
| CD38 x CD3 | AMG424 * | Fc region | 1 | 27 | N/A | N/A | N/A | NCT03445663 [24] |
| CD38 x CD3 | GBR 1342 | BEAT® platform | 1 | N/A | N/A | N/A | N/A | NCT03309111 [43] |
| CD19 x CD3 | Blinatumomab ** | BiTE | 1 | 6 | N/A | N/A | N/A | NCT03173430 [33] |
| FcRH5 x CD3 | Cevostamab | IgG1-based Fc region | 1 | 53 | 53% (18 of 34 patients, IV) at doses ≥3.6/20 mg | 86% (6 of 7 evaluable patients) across all cohorts | 76% (40 of 53 patients): Grade 1 = 18%; Grade 2 = 40%; Grade 3 = 2% | NCT03275103 [44] |
| GPRC5D x CD3 | Talquetamab | IgG4 Fc region | Phase 1 | Total of 184 patients with 30 participants treated at the RP2D | 70% (21 of 30 patients) at the RP2D (SC 405 µg/kg, with 10.0 and 60.0 µg/kg step-up doses) | 67% (4 of 6 patients) across both IV and SC cohorts including 1 patient from the RP2D cohort | 73% (22 of 30 patients) at the RP2D: Grade 1 = 60%; Grade 2 = 10%; Grade 3 = 3% | NCT03399799 [45] |
MTD = maximum tolerated dose; CRS = cytokine release syndrome; RP2D = recommended phase 2 dose; IV = intravenously administrated; SC = subcutaneously administered; N/A = not available; * Terminated due to sponsor business decision; ** Terminated due to slow accrual.