Table 3.
Clinical trials of various Antibody Drug Conjugates in AML and MDS.
| Study | Trial Identification | Mechanism | Study Population | Study Status | Results | MRD Status | Adverse Effects | Ref |
|---|---|---|---|---|---|---|---|---|
| Phase 1 trial of vadastuximab talirine monotherapy (VT) with HMA in patients with CD 33-positive AML patients. | NCT01902329 | Anti-CD33 | AML-CR with initial induction/consolidation or R/R-AML or declined treatment with high dose induction/consolidation | Completed | The composite remission rate (CR + CRi) was 70%. Median PFS and OS were 7.7 and 11.3 months, respectively | 51% were MRD negative | Increased hematological toxicity | [105] |
| Phase 3 Study of VT versus placebo in combination with azacitidine or decitabine in the treatment of older patients with newly diagnosed AML | NCT02785900 | Anti-CD33 | Newly diagnosed AML | Terminated | N/A | N/A | Higher rate of death, including fatal infections in VT versus control arm | N/A |
| Phase 1, open label study of IMGN779 in adult patient with R/R CD 33 positive AML | NCT02674763 | Anti-CD33 | R/R AML | Completed | 11/27 patients (41%) who received IMGN779 had a >30% reduction in bone marrow blasts | N/A | Febrile neutropenia, epitaxis, nausea, diarrhea, fatigue, abdominal pain and hypokalemia. Grade 3+ adverse events, most frequent: febrile neutropenia, bactermia, pneumonia, and anemia | [106] |
| Dose-escalation safety and pharmacokinetic study of AVE9633 | NCT00543972 | Anti-CD33 | R/R AML | Terminated | Terminated due to absence of evidence of clinical activity to toxic doses | N/A | N/A | N/A |
| Phase 1/2 multicenter, open label study of IMGN632 monotherapy sdminstered intravenously in patients with CD 123-positive hematological malignancies | NCT03386513 | Anti-CD 123 | CD 123-postiive AML and other CD123-positive hematological malignancies | Recruiting | Four (33%) achieved an OR including one CR and three CRi | N/A | Decreased appetite, diarrhea, nausea, febrile neturopenia, peripheral edema, hypotension, sinus tachycardia | [107] |
| Phase 1, dose escalation and dose expansion trial of SGN-CD123A to evaluate safety, tolerability, and anti-tumor efficacy |
NCT02848248 |
Anti-CD 123 | R/R AML | Terminated | NA | N/A | Terminated due to safety concern | N/A |
| A Phase 1/2 study of SL-401 as consolidation therapy for adults with adverse risk AML in first CR and/or evidence of MRD in first CR | NCT02270463 | Anti-CD 123 | Adverse risk AML | Completed | N/A | N/A | N/A | N/A |
| Phase 1 trial of SL-401 in combination with azacitidine or azacitidine/venetoclax in AML, high-risk MDS or blastic plasmacytoid dendritic cell neoplasm | NCT03113643 | Anti-CD123 | AML, high-risk MDS, blastic plasmacytoid dendritic neoplasm | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1 study combining escalating doses of radiolabeled BC8 antibody with fludarabine, and low-dose total-body irradiation followed by donor stem cell transplant and immunosuppresion therapy in treating older patients with advanced AML or high-risk MDS | NCT00008177 | Anti-CD45 | AML/High Risk MDS | Recruiting | CR in all patients and engraftment by day 28 of transplant. Median OS and DFS among all 58 patients—199 days and 159 days, respectively, and among the 21 patients treated at the MTD, 206 and 189 days, respectively | N/A | Infusion toxicites, chills, nausea, vomiting, respiratory symptoms such as throat or chest tightness, and hypotension | [108] |
| Phase 3 study of I 131 monoclonal antibody prior to allogeneic HSCT versus conventional care in older subjects with active, R/R AML | NCT02665065 | Anti-CD45 | Older patients with R/R AML | Recruiting | N/A | N/A | N/A | N/A |
| Phase 1 trial of brentuximab vedotin with re-induction chemotherapy with relapsed, CD30-positive AML | NCT01830777 | Anti-CD30 | R/R AML | Completed | N/A | N/A | N/A | N/A |
| Phase 2, open-label study of brentuximab vedotin in patients with CD30-positive nonlymphomatous malignancies | NCT01461538 | Anti-CD30 | AML, ALL or MDS | Completed | N/A | N/A | N/A | N/A |
| Phase 1/2 study of weekly schedule of brentuximab vedotin alone and in combination with azacytidine in CD 30 positive R/R AML | NCT01830777 | Anti-CD30 | R/R AML | Terminated due to slow accrual | N/A | N/A | N/A | N/A |
Abbreviations: CR, complete remission; Cri, complete remission with incomplete count recover; OR, objective response; OS, overall survival; DFS, disease-free survival; MTD, maximum tolerated dose; PFS, progression-free survival.