Table 1.
List of phase I and II trials exploring mAbs in multiple myeloma (MM)
| MAb Class | Molecule (Targets) | Study | Treatment | Setting | Toxicities (≥G3) | ORR (MRD Negativity Rate; NGS, Sensitivity 10−5) | PFS | OS |
|---|---|---|---|---|---|---|---|---|
| Naked | Daratumumab (anti-CD38) | GEN501 + SIRIUS [24,25] NCT00574288 NCT01985126 |
Daratumumab single agent | RRMM | Anemia (17.6%); back pain g3 (2.7%); fatigue g3 (2%) | 31.1% | 4 | 20.1 |
| Naked | Daratumumab (anti-CD38) | EQUULEUS [26] NCT01998971 |
Dara-Poma-dex | RRMM | Neutropenia (77%); fatigue (12%); dyspnea (8%) | 60% (6%) | 8.8 | 17.5 |
| Naked | Daratumumab (anti-CD38) | GRIFFIN [27] NCT02874742 |
Dara-VRd vs. VRd | NDMM | Neutropenia (41.4% vs. 21.6%); peripheral neuropathy (7.1% vs. 7.8%); diarrhea (7.1% vs. 3.9%) | 99% vs. 91.8% (51% vs. 20.4%) | NR vs. NR | NR vs. NR |
| Naked | Daratumumab (anti-CD38) | PAVO [28] NCT02519452 | Subcutaneous administration of daratumumab single agent* | RRMM | Anemia (15.6%); hypertension (8.9%); pneumonia (4.4%); hyponatremia (4.4%); respiratory syncytial virus infection (4.4%); device-related infection (4.4%) | 42.2% | NA | NA |
| Naked | Isatuximab (anti-CD38) |
TCD11863 [29] NCT01749969 |
Isa-Rd | RRMM | Neutropenia (60%); pneumonia (9%); fatigue (7%) | 56% | 8.5 | NR |
| Naked | Isatuximab (anti-CD38) |
TCD14079 [30] NCT02283775 |
Isa-Pd | RRMM | Neutropenia (84%); pneumonia (18%); fatigue (7%); urinary tract infection (7%); traumatic fracture (7%); syncope (7%); dyspnea (7%); hypertension (7%) | 62.2% (0%) * |
17.6 | NR |
| Naked | Isatuximab (anti-CD38) | GMMC-CONCEPT [31] NCT03104842 |
Isa-KRD | High risk NDMM | Neutropenia (34%); hypertension (12%); cardiac failure (4%) | 100% (40%) ** | NA | NA |
| Naked | MOR202 (anti-CD38) | MOR202C101 [32] NCT01421186 |
MOR202+dexamethasone | RRMM | Anemia (39%); hypertension (11%); bronchitis (6%); pneumonia (6%); hyperglycemia (6%) | 28% | 8.4 | NA |
| MOR202-Rd | Lymphopenia (59%); hypophosphatemia (12%); hypertension (12%) | 65% | NR | NA | ||||
| MOR202-Pd | Neutropenia (71%); pneumonia (24%); hypertension (19%) | 48% | 17.5 | NA | ||||
| Naked | TAK-079 (anti-CD38) | TAK-079–1501 [33] NCT03439280 |
TAK-079 single agent | RRMM | Neutropenia (5%); parainfluenza virus infection (5%); diverticulitis (5%) | 33% | NR | NA |
| Naked | Elotuzumab (anti-SLAMF7) | ELOQUENT-3 [34] NCT02654132 |
Elo-Pd vs. Pd | RRMM | Neutropenia (13% vs. 27%); infections (13% vs. 22%); hyperglycemia (8% vs. 7%) | 53% vs. 26% | 10.3 vs. 4.7 | NA |
| Naked | Pembrolizumab (anti-PD-1) | KEYNOTE-023 [35] NCT02036502 |
Pembrolizumab-Rd | RRMM | Neutropenia (27.4%); hyperglycemia (6.5%); pneumonia (6.5%); atrial fibrillation (3.2%); insomnia (3.2%) | 44% | 7.2 | NR |
| Naked | Pembrolizumab (anti-PD-1) | HP-00061522 [36] NCT02289222 |
Pembrolizumab-Pd | RRMM | Neutropenia (42%); hyperglycemia (21%); fatigue (15%); pneumonia 15%) | 60% | 17.4 | NR |
| ADC | Belantamab mafodotin (anti-BCMA, monomethyl auristatin F payload) | DREAMM-1 [37,38] NCT02064387 |
Belamaf single agent | RRMM | Thrombocytopenia (35%); keratopathy (14%); diarrhea (12%) | 60% *** | 12 | NR |
| ADC | Belantamab mafodotin (anti-BCMA, monomethyl auristatin F payload) | DREAMM-2 [39,40,41,42] NCT03525678 |
Belamaf single agent (data on the 2.5 mg/kg cohort are shown) | RRMM | Thrombocytopenia (20%); keratopathy (27%); hypercalcemia (7%) | 31% | 2.9 | 14.9 |
| ADC | Belantamab mafodotin (anti-BCMA, monomethyl auristatin F payload) | DREAMM-6 [43] NCT03544281 |
Belamaf-Vd | RRMM | Thrombocytopenia (61%); keratopathy (56%); hypercalcemia (7%) | 78% | NA | NA |
| BiAb | AMG 420 (anti-BCMA/anti-CD3) | 1351.1 [44] NCT02514239 |
AMG 420 single agent | RRMM | Infections (24%) neuropathy (5%) CRS (2%) |
70% *** | NA | NA |
| BiAb | PF-3135 (anti-BCMA/anti-CD3) | C1071001 [45] NCT03269136 |
PF-3135 single agent | RRMM | Increased liver enzymes (6%) neutropenia (6%), lymphopenia (6%) | 0% *** | NA | NA |
| BiAb | CC-93269 (anti-BCMA/anti-CD3) | CC-93269-MM-001 [46] NCT03486067 |
CC-93269 single agent | RRMM | Neutropenia (43%), infections (30%), general physical deterioration (10%) | 89% *** (78%) ** | NA | NA |
| BiAb | Teclistamab (anti-BCMA/anti-CD3) |
CR108206 [47] NCT03145181 |
Teclistamab single agent | RRMM | Neutropenia (48%), infections (21%), neurotoxicity (3%) | 67% *** | NA | NA |
* Sensitivity 10−6; ** Flow. *** At the maximum tolerated dose (MTD) or at the highest dose tested when the MTD has not yet been reached. Abbreviations: MAb, monoclonal antibody; G, grade; ORR, overall response rate; CRS, cytokine release syndrome; MRD, minimal residual disease; NGS, next-generation sequencing; PFS, progression-free survival; OS, overall survival; RRMM, relapsed/refractory multiple myeloma; NDMM, newly diagnosed multiple myeloma; Dara, daratumumab; P, Poma, pomalidomide; d, dex, dexamethasone; V, bortezomib; R, lenalidomide; NR, not reached; NA, not available; Isa, isatuximab; SLAMF7, signaling lymphocytic activation molecule family 7; Elo, elotuzumab; PD-1, programmed cell death protein 1; BCMA, B-cell maturation antigen; belamaf, belantamab mafodotin; ADC, antibody–drug conjugate; BiAb, bispecific antibody.