Background：Camidanlumab tesirine is an antibody-drug conjugate against CD25, an antigen expressed in several malignancies, including acute lymphoblastic leukemia ALL and acute myeloid leukemia AML. This open-label, dose-escalation and -expansion study NCT02588092 assessed the safety, activity, pharmacokinetics PK, and immunogenicity of camidanlumab tesirine in patients with relapsed/refractory ALL/AML. A total of 35 patients 34 AML and 1 ALL were enrolled and received camidanlumab tesirine intravenously at 3-92 μg/kg once every three weeks Q3W, n = 26 or 30 or 37.5 μg/kg every week QW, n = 9. One dose-limiting toxicity of maculopapular rash occurred in the 30 μg/kg QW group; the maximum tolerated dose was not reached. No additional safety concerns or adverse events AEs of interest were identified. The most common >10 % of patients Grade ≥3 treatment-emergent AEs were febrile neutropenia 25.7 %, lymphopenia, neutropenia, thrombocytopenia or fatigue all 14.3 %, pneumonia, increased gamma-glutamyltransferase, and hypophosphatemia each 11.4 %. No signal for serious immune-related AEs such as Guillain-Barré syndrome/polyradiculopathy was observed and there was no evidence of immunogenicity. PK showed rapid clearance with apparent half-life <2 days for conjugated and total antibody, suggesting that Q3W dosing may be insufficient for therapeutic efficacy, and prompting exploration of a QW schedule. Two patients achieved complete responses with incomplete hematologic recovery; one each at 30 and 37.5 μg/kg QW. The trial was terminated during dose escalation due to programmatic reasons other than safety. Hence, recommended dose was not determined.
Alternative Names：ADCT-301unconjugated, HuMax-TAC-ADC,
