Table 2 Clinical trials of bispecific antibodies in hematologic malignancies
From: Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies
Drug | Disease | Target | Phase | Identifier | Dose | Number | Response | Adverse events |
|---|---|---|---|---|---|---|---|---|
Blinatumomab | R/R Ph + ALL | CD19/CD3 | II | NCT02000427 | 9 mg/day (first 7 days) 28 mg/day (following days) | n = 45 | CR/CRh rate = 35.6% | AE(common): pyrexia (58%), febrile neutropenia (40%), and headache (31%) |
|  |  |  |  |  |  |  |  | AE(grade ≥ 3): febrile neutropenia (27%), thrombocytopenia (22%), and anemia (16%) |
|  | R/R B-ALL | CD19/CD3 | II | NCT01466179 | 9 μg/day (first 7 days) | n = 189 | CR/CRh rate = 43% | AE (common): pyrexia (113, 60%), headache (34%), febrile neutropenia (28%), peripheral oedema (26%), nausea (24%), hypokalaemia (24%), constipation (21%), anemia (20%) |
|  |  |  |  |  | 28 μg/day (following days) |  |  | AE (grade ≥ 3): febrile neutropenia (25%), neutropenia (16%), anemia (14%) |
|  | R/R NHL | CD19/CD3 | I | Not applicable | 5 μg/m2/d (week 1) | n = 9 | ORR = 56% | AE (common): pyrexia (81.8%), fatigue (54.5%), constipation (36.4%), headache (36.4%), tremor (36.4%), and weight increase (36.4%) |
|  |  |  |  |  | 15 μg/m2/d (week 2) |  |  |  |
|  |  |  |  |  | 60 μg/m2/d (following days) |  |  |  |
MGD006 | R/R AML | CD123/CD3 | I/II | NCT02152956 | 500 ng/kg/day | n = 30 | CR/CRh rate = 26.7% | AE (common): CRS (mild to moderate signs/symptoms) (81%), |
|  |  |  |  |  |  |  | CR/CRh/CRi rate = 30.0% | Grade 3 events: (8%) |
XmAb14045 | R/R AML | CD123/CD3 | I | NCT02730312 | 1.3 µg/kg/week and 2.3 µg/kg/week | n = 63 | CR/CRi rate = 23% | AE (common): fatigue (31%), febrile neutropenia (30%), peripheral edema (30%), cough (23%), elevated hepatic transaminases (19%), pneumonia (17%), stomatitis (14%), hyperglycemia (13%), sepsis (11%) |
AMG 330 | R/R AML | CD33-CD3 | I | NCT02520427 | 0.5–720 µg/day | n = 42 | ORR = 19% | AE (common): cytokine release syndrome (67%), nausea (20%) |
AMG420 | R/R MM | BCMA/CD3 | I | NCT02514239 | 400 µg/d recommended | n = 42 | ORR = 31% | AE (common): infections, polyneuropathy |
REGN1979 | R/R FL (Gr 1-3a) | CD20/CD3 | I | Not applicable | 5-320 mg/week | n = 14 | ORR = 93% | AE (common): pyrexia, CRS, chills, infections and infestations, fatigue, increased C-reactive protein, anemia |
|  | R/R DLBCL |  |  |  | 5-12 mg/week | n = 11 | ORR = 18.2% |  |
|  |  |  |  |  | 18–40 mg/week | n = 11 | ORR = 54.5% |  |
|  |  |  |  |  | 80 mg/week | n = 3 | ORR = 100% |  |
|  |  |  |  |  | 160 mg/week | n = 3 | ORR = 33.3% |  |
RG6026 | R/R B-NHL | CD20/CD3 | I | NCT03625037 | 300–1800 µg | n = 24 | ORR = 8/24 | AE (common): pyrexia, neutropenia and cytokine release syndrome |
|  | R/R FL |  |  |  | 300–1800 µg | n = 5 | ORR = 3/5 |  |
Mosunetuzumab | Indolent NHL | CD20/CD3 | I/Ib | NCT02500407; GO29781 | inferior to 1/2/60 mg (Cycle 1 Day 1, 8, and 15) | n = 64 | ORR = 64.1% | AE(common):CRS(28.4%), |
| Â | Â | Â | Â | Â | Â | Â | CRR42.2% | headache (14.7%), insomnia (10.1%), dizziness (9.2%) |
|  | Aggressive NHL |  |  |  |  | n = 119 | ORR34.7% |  |
|  |  |  |  |  |  |  | CRR = 18.6% |  |