Non-BCMA–targeted TCE therapies and their respective clinical trials
| Target . | GPRC5D . | GPRC5D + anti-CD38mAb . | GPRC5D + BCMA . | GPRC5D . | FcRH5 . |
|---|---|---|---|---|---|
| Drug/study | Talquetamab MonumenTAL-125 | Talquetamab + daratumumab TRIMM-226 | Talquetamab + teclistamab RedirecTT-127 | Forimtamig (RG6234)28 | Cevostamab29 |
| Phase | 2 | 2 | 1b | 1 | 1 |
| Cohorts | 1: SC 0.4 mg/kg QW 2: SC 0.8 mg/kg Q2W 3. Prior T-cell redirection, either dose | SC 0.4 mg/kg QW or SC 0.8 mg/kg Q2W + SC Dara 1800 mg per schedule | RP2D: SC Tec 3.0 mg/kg Q2W + SC tal 0.8 mg/kg Q2W SC (RP2D, n = 34; All dose levels, n = 93) | 1: IV 6 μg –10 mg 2: SC 30 μg –7.2 mg | 1: C1D1 (IV 0.05-3.6 mg), target dose (0.15-198 mg) C1D8 × 17 cycles 2: C1D1 (IV 0.3-1.2 mg), C1D8 (3.6 mg), target dose (60-160 mg) on C1D15 × 17 cycles |
| Median age (range), y | — | 63 (37-81) | 67 (39-81) | (Cohort 1,2) 62 (27-78), 64 (46-79) | 64 (33-82) |
| Med follow-up (range), mo | 8.6-14.9 | 11.5 | 14.4 | (Cohort 1,2) 7.1, 3.9 | 6.1 |
| Median prior LOTs (range) | 5-6 | 5 (2-16) | 5 (1-11) | (Cohort 1,2) 5 (2-15), 4 (2-14) | 6 (2-18) |
| Previous BCMA therapies, % | 15 (cohort 1) 11 (cohort 2) 12 (cohort 3) | 54 (exposed) 38 (refractory) | — | (Cohort 1,2) 19.6, 20.4 | 33.8 |
| Cohort size (no. of patients) | 143, 145, 51 (Cohort 1,2,3) | 65 | 63 | (Cohort 1,2) 51, 54 | 160 |
| Efficacy, % | (Cohort 1,2,3) | 78 (74/64 if prior BCMA exposed/ refractory) | 84 | (Cohort 1,2) | 54.5 (160 mg dose), 36.7 (90 mg dose), 36.4 (prior anti-BCMA) |
| ORR | 74, 73, 63 | 45 | 34 | 71.4, 60.4 | — |
| CR/sCR (%) | - | 19 | NR | 28.5, 18.8 | — |
| mPFS, mo | 7.5, 11.9, 5.1 | (1-y PFS 76%) | NR | — | — |
| OS | — | 1-y OS: 93% | — | — | |
| DOR | — | — | — | ||
| Safety, % | (Cohort 1,2,3) | 78/0 | (At RP2D) | (Cohort 1,2) | 80/1.3 |
| CRS all grades/G3+ | 79,75,77/- | 5/0 | 81/3 | 82.4,77.8/2,1.9 | 13/- |
| ICANS all grades/G3+ | 11,11,3/- | 38/26 | 2/- | 8.6/1.9 | 18.1/16.3 |
| Neutropenia all grades/G3+ | — | Anemia 52/- | 76/75 | — | 31.9/21.9 |
| Anemia all grades/G3+ | — | — | 60/43 | — | — |
| Thrombocytopenia all grades/G3+ | — | — | — | ||
| Other/other G3+ | Skin AE 56,71,69 Nail-related AE 54,53,61 Dysgeusia 50,48,61 Infections 58,65,71/22,16,26 | Skin exfoliation 45/- Dysgeusia 75/- Infections 63/25 | Dysgeusia 47.1/- Skin toxicity 52.9/- Nail disorders 41.2/- Infections -/38.2 | Skin AE 72.5, 81.5/11.8,14.8 Hair and nail-related AE 17.6, 22.2/0,0 GI/mucosa-related AE 70.6,74.1/0,5.6 | Infections 42.5/18.8 Hemophagocytic lymphohistiocytosis 0/0.6 (G5) |
| Target . | GPRC5D . | GPRC5D + anti-CD38mAb . | GPRC5D + BCMA . | GPRC5D . | FcRH5 . |
|---|---|---|---|---|---|
| Drug/study | Talquetamab MonumenTAL-125 | Talquetamab + daratumumab TRIMM-226 | Talquetamab + teclistamab RedirecTT-127 | Forimtamig (RG6234)28 | Cevostamab29 |
| Phase | 2 | 2 | 1b | 1 | 1 |
| Cohorts | 1: SC 0.4 mg/kg QW 2: SC 0.8 mg/kg Q2W 3. Prior T-cell redirection, either dose | SC 0.4 mg/kg QW or SC 0.8 mg/kg Q2W + SC Dara 1800 mg per schedule | RP2D: SC Tec 3.0 mg/kg Q2W + SC tal 0.8 mg/kg Q2W SC (RP2D, n = 34; All dose levels, n = 93) | 1: IV 6 μg –10 mg 2: SC 30 μg –7.2 mg | 1: C1D1 (IV 0.05-3.6 mg), target dose (0.15-198 mg) C1D8 × 17 cycles 2: C1D1 (IV 0.3-1.2 mg), C1D8 (3.6 mg), target dose (60-160 mg) on C1D15 × 17 cycles |
| Median age (range), y | — | 63 (37-81) | 67 (39-81) | (Cohort 1,2) 62 (27-78), 64 (46-79) | 64 (33-82) |
| Med follow-up (range), mo | 8.6-14.9 | 11.5 | 14.4 | (Cohort 1,2) 7.1, 3.9 | 6.1 |
| Median prior LOTs (range) | 5-6 | 5 (2-16) | 5 (1-11) | (Cohort 1,2) 5 (2-15), 4 (2-14) | 6 (2-18) |
| Previous BCMA therapies, % | 15 (cohort 1) 11 (cohort 2) 12 (cohort 3) | 54 (exposed) 38 (refractory) | — | (Cohort 1,2) 19.6, 20.4 | 33.8 |
| Cohort size (no. of patients) | 143, 145, 51 (Cohort 1,2,3) | 65 | 63 | (Cohort 1,2) 51, 54 | 160 |
| Efficacy, % | (Cohort 1,2,3) | 78 (74/64 if prior BCMA exposed/ refractory) | 84 | (Cohort 1,2) | 54.5 (160 mg dose), 36.7 (90 mg dose), 36.4 (prior anti-BCMA) |
| ORR | 74, 73, 63 | 45 | 34 | 71.4, 60.4 | — |
| CR/sCR (%) | - | 19 | NR | 28.5, 18.8 | — |
| mPFS, mo | 7.5, 11.9, 5.1 | (1-y PFS 76%) | NR | — | — |
| OS | — | 1-y OS: 93% | — | — | |
| DOR | — | — | — | ||
| Safety, % | (Cohort 1,2,3) | 78/0 | (At RP2D) | (Cohort 1,2) | 80/1.3 |
| CRS all grades/G3+ | 79,75,77/- | 5/0 | 81/3 | 82.4,77.8/2,1.9 | 13/- |
| ICANS all grades/G3+ | 11,11,3/- | 38/26 | 2/- | 8.6/1.9 | 18.1/16.3 |
| Neutropenia all grades/G3+ | — | Anemia 52/- | 76/75 | — | 31.9/21.9 |
| Anemia all grades/G3+ | — | — | 60/43 | — | — |
| Thrombocytopenia all grades/G3+ | — | — | — | ||
| Other/other G3+ | Skin AE 56,71,69 Nail-related AE 54,53,61 Dysgeusia 50,48,61 Infections 58,65,71/22,16,26 | Skin exfoliation 45/- Dysgeusia 75/- Infections 63/25 | Dysgeusia 47.1/- Skin toxicity 52.9/- Nail disorders 41.2/- Infections -/38.2 | Skin AE 72.5, 81.5/11.8,14.8 Hair and nail-related AE 17.6, 22.2/0,0 GI/mucosa-related AE 70.6,74.1/0,5.6 | Infections 42.5/18.8 Hemophagocytic lymphohistiocytosis 0/0.6 (G5) |
G3, grade 3; GI, gastrointestinal; NR, not reached; Q2W, once every 2 weeks; QW, once weekly; RP2D, recommended phase 2 dose.