Table 2 Clinical trials of monoclonal antibodies, ADCs and BiTEs
Agent | Trial ID | Intervention | Disease type | Target | Efficacy data | Adverse event | References | |
|---|---|---|---|---|---|---|---|---|
Monoclonal antibodies | Daratumumab (Dara) | NCT01985126 SIRIUS | Single agent | RRMM | CD38 | ORR 30.4%, mOS 20.5 mon | Grade 3 or 4 AEs:fatigue (3%), anemia (24%), thrombocytopenia (19%), neutropenia (12%), back pain (3%) | [42] |
NCT02136134 CASTOR | Dara + BTZ + DEX versus BTZ + DEX | RRMM | CD38 | Better PFS (16.7 mon versus 7.1 mon, p < 0.0001), better ORR (83.8% vs. 63.2%, p < 0.0001) | Grade 3 or 4 AEs: thrombocytopenia (45.3% vs. 32.9%), anemia (14.4% vs. 16.0%), neutropenia (12.8% vs. 4.2%) | [43] | ||
NCT02076009 POLLUX | Dara + Len + DEX versus Len + DEX | RRMM | CD38 | Better PFS (not reached versus 17.5 mon, p < 0.0001), and ORR (92.9% vs. 76.4%, p < 0.0001) | Grade 3 or 4 AEs: neutropenia (51.9% vs. 37%), anemia (12.4% vs. 19.6%), thrombocytopenia (12.7% vs. 13.5%), lymphopenia (5.3% vs. 3.6%) | [44] | ||
NCT03158688 CANDOR | Dara + Carfilzomib + DEX versus Carfilzomib + DEX | RRMM | CD38 | Better ORR (84.3% vs. 74.7%, p = 0.004) | Grade 3 or 4 AEs: thrombocytopenia (24% vs. 16%), hypertension (18% vs. 13%), anemia (17% vs. 15%), pneumonia (13% vs. 9%), neutropenia (9% vs. 6%) | [46] | ||
NCT02195479 ALCYONE | Dara + Melphalan + Prednisone versus BTZ + Melphalan + Prednisone | NDMM | CD38 | Better PFS (36.4 mon vs. 19.3 mon, p < 0.0001) and OS (78% vs. 67.9%) | Neutropenia (49.7% vs. 52.5%), thrombocytopenia (48.8% vs. 53.7%), peripheral sensory neuropathy (28.3% vs. 34.2%), anemia (28% vs. 37.6%) | [47] | ||
NCT02252172 MAIA | Dara + Len + DEX versus Len + DEX | NDMM | CD38 | Better PFS (not reached vs. 33.8 mon, p < 0.0001) | Grade 3 or 4 AEs: neutropenia (50.0% vs. 35.3%), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), pneumonia (13.7% vs. 7.9%) | [48] | ||
NCT02874742 GRIFFIN | Dara + Len + BTZ + DEX versus Len + BTZ + DEX | NDMM | CD38 | Improved ORR (99% vs. 92%, p = 0.01), sCR (42.4% vs. 32%, p = 0.068), ≥ VGPR (91% vs. 73%, p = 0.001), ≥ CR (52% vs. 42%) | Grade 3 or 4 AEs: neutropenia (41.4% vs. 21.6%), lymphopenia (23.2% vs. 21.6%), thrombocytopenia (16.2% vs. 8.8%), leukopenia (16.2% vs. 6.9%), pneumonia (8.1% vs. 10.8%) | [49] | ||
NCT02541383 CASSIOPEA | Dara + BTZ + Thalidomide + DEX versus BTZ + Thalidomide + DEX | NDMM | CD38 | Better sCR rate (29% versus 20%, p = 0.001), ≥ CR (39% vs. 26%, p < 0.0001), MRD negativity (64% vs. 44%, p < 0.0001), PFS rate of 18 mon (93% vs. 85%, p < 0.0001) | Grade 3 or 4 AEs: neutropenia (28% vs. 15%), lymphopenia (17% vs. 10%), stomatitis (13% vs. 16%) | [8] | ||
Elotuzumab (Elo) | NCT02654132 ELOQUENT-3 | Elo + Pomalidomide + DEX versus Pomalidomide + DEX | RRMM | SLAMF7 | Better PFS (10.3 mon vs. 4.7 mon), ORR (53% vs. 26%) | Grade 3 or 4 AEs: neutropenia (13% vs. 27%), anemia (10% vs. 20%), hyperglycemia (8% vs. 7%) | [53] | |
NCT01478048 | Elo + BTZ + DEX versus BTZ + DEX | RRMM | SLAMF7 | Better PFS (9.7 mon vs. 6.9 mon), ORR (66% vs. 63%, ≥ VGPR (36% vs. 27%) | No additional clinically significant AEs occurred. Grade 1/2 infusion reaction rate was low | [54] | ||
NCT 02,272,803 | Elo + Len + DEX versus Len + DEX | NDMM | SLAMF7 | ORR (88% vs. 74%), ongoing | Grade 3 or 4 AEs: neutropenia (18% vs. 7%), leukopenia (15% vs. 0%). Any-grade infections (73% vs. 62%) | [55] | ||
NCT01668719 SWOGS1211 | Len + BTZ + DEX with versus without Elo (maintenance therapy) | NDMM | SLAMF7 | Similar PFS (31 mon vs. 34 mon, p = 0.449), ongoing | Fatigue (100%), peripheral sensory neuropathy (83%), edema (83%), lymphopenia (66%), leukopenia (50%) | |||
NCT02495922 GMMG-HD6 | Elo + BTZ + Len + DEX (induction therapy) | NDMM | SLAMF7 | Similar ORR (82.4% vs. 85.6%, p = 0.35), similar ≥ VGPR (58.3% vs. 54.0%, p = 0.35) | Ongoing | [58] | ||
Isatuximab (Isa) | NCT02990338 ICARIA-MM | Isa + Pomalidomide + DEX versus Pomalidomide + DEX | RRMM | CD38 | Better PFS (11.53 mon vs. 6.47 mon, p = 0.001), ORR (60.4% vs. 35.3%), high-risk patients still had benefit | ALL grades: infusion reactions (56% vs. 0%), respiratory infection (43% vs. 26%), diarrhea (39% vs. 29%), similar anemia and thrombocytopenia; grade 3 or 4 AEs (87% vs. 71%) | ||
NCT03275285 IKEMA | Isa + Carfilzomib + DEX versus Carfilzomib + DEX | RRMM | CD38 | Better PFS (NR vs. 17.5 mon, p = 0.0007), ORR (86.6% vs. 82.9%), ≥ VGPR (72.6% vs. 56.1%, p = 0.193) | Grade 3 or 4 AEs: (76.8 vs. 67.2%) | [62] | ||
MOR202 | NCT01421186 | MOR202 monotherapy versus MOR202 + DEX versus MOR202 + DEX + Pomalidomide versus MOR202 + DEX + Len | RRMM | CD38 | Ongoing, maximum tolerated dose was not reached | Grade 3 or 4 AEs: lymphopenia (38%), neutropenia (33%), leukopenia (30%) | [63] | |
Antibody−drug conjugates | GSK2857916 | NCT03525678 DREAMM-2 | Single agent | RRMM | BCMA | ORR 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort; mOS was not reached | Grade 3 or 4 AEs: keratopathy (27% in the 2.5 mg/kg cohort, 21% in the 3.4 mg/kg cohort), thrombocytopenia (20% and 33%), anemia (20% and 25%) | [68] |
| Â | Lorvotuzumab mertansine | NCT00346255 | Single agent | RRMM | CD56 | PR 5.7%; minor response 11.4%; SD 42.9%; mDOR 15.5 mon; PFS 6.5 mon | Grade 3 or 4 AEs: headache (5.4%), peripheral neuropathy (2.7%), neutropenia (2.7%) | [70] |
BiTEs | AMG 420 | NCT02514239 | Single agent | RRMM | BCMA/CD3 | sCR: 5; VGPR:1; PR:1; ORR 70%; DOR: 5.6–10.4 mon | Grade 3 or 4 AEs: infections (28%), polyneuropathy (4%) | [96] |
| Â | CC-93269 | NCT03486067 | Single agent | RRMM | BCMA/CD3 | ORR 83.3% | Grade 3 or 4 AEs: neutropenia (52.6%), anemia (42.1%), infections (26.3%), thrombocytopenia (21.1%), 1 died of CRS | [97] |