Table 2.
Clinical trials of various antibody constructs (BiTE and TriKE) in therapy of MDS and AML.
| Study | Trial Identification | Mechanism | Study Population | Study Status | Results | MRD Status | Adverse Effects | Ref |
|---|---|---|---|---|---|---|---|---|
| Bispecific T-Cell Engagers (BiTE) | ||||||||
| Phase 1 dose escalation (AMG 330) |
NCT02520427 | Bispecific mAb w/ specificity to CD33 and CD3ε | R/R AML | Recruiting | CR/CRi: 16% | N/A | CRS: 67% | [92] |
| Phase 1b dose escalation, AMG 330+ pembrolizumab | NCT04478695 | Bispecific mAb w/ specificity to CD33 and CD3ε + PD-L inhibitor | R/R AML | Terminated | N/A | N/A | N/A | N/A |
| Phase 1 dose escalation (AMG 427) |
NCT03541369 | Bispecific mAb w/ specificity to CD3ε and FLT3 scFv | R/R AML | Active, Recruiting | N/A | N/A | N/A | [95] |
| Phase 1 dose escalation (AMV 564) |
NCT03144245 | Bispecific mAb w/ specificity to CD33 and CD3ε- tetravalent | R/R AML | Active, Not Recruiting | Reductions in BM blasts ranging from 13 to 38% in 6 of 9 evaluable patients | N/A | Febrile neutropenia in 25% | [90] |
| Phase 1 dose escalation Vibecotamab (XmAb14045) | NCT02730312 | Bispecific mAb w/ specificity to CD123/CD3ε | R/R AML | Active, Recruiting | ORR: CR/CRi/MLFS: 14% SD:71% Low disease burden: RR 26% |
N/A | CRS: 58% | [96] |
| Phase 1 dose escalation (AMG 673) | NCT03224819 | Half-life extended bispecific T-cell engager—HLE BiTE to CD33 and CD3 | R/R AMl | Active, Not Recruiting | ORR 44% decrease in BM blasts, 22% with >50% reduction and 3% with >85% reduction in BM blasts | N/A | CRS: 50%, | [93] |
| Dual Affinity Re-Targeting Molecules DART (BiTE) | ||||||||
| Phase 1/2 Flotetuzumab (MGD006) | NCT02152956 | Bispecific mAb w/ specificity to CD123/CD3ε | PIF or R/R AML or Intermediate-2/High Risk MDS |
Active, Recruiting | CR/CRh: 24% Median OS (in patients that achieved CR/CRh): 10.2 m |
NA | IRR/CRS in PIF/ER population (n = 30): 100% (all grades), Gr > 3: 3.3% | [97] |
| Tri-Specific Killer Engager (TriKE) | ||||||||
| Phase 1—GTB-3550 TriKE | NCT03214666 | Tri-Specific Killer Engager-CD16/IL-15/CD33 | PIF/ R/R AML, High risk MDS | Active, recruiting | 4 pts enrolled, 3 completed, 2 w/SD, 1 w/POD. | NA | No toxicity reported. | [98] |
Abbreviations: R/R, relapsed refractory; CR, complete remission; CRi, complete remission with incomplete count recovery; CRh, complete remission with partial hematologic recovery; MLFS, morphologic leukemia-free state; CRS, cytokine release syndrome; BM, bone marrow; LFT, liver function tests; POD, progression of disease; RR, response rate; PIF, primary induction failure; ER, early relapse; MDS, myelodysplasia; IRR, infusion-related reactions.