Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study

Aaron D. Goldberg, Ehab Atallah, David Rizzieri, Roland B. Walter, Ki Young Chung, Alexander Spira, Wendy Stock, Martin S. Tallman, Hans G. Cruz, Joseph Boni, Karin E.G. Havenith, Grace Chao, Jay M. Feingold, Jens Wuerthner, Melhem Solh

Research output: Contribution to journalArticlepeer-review

Abstract

There is a significant need for improved therapeutics in older patients with acute leukemia. 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.

Original languageEnglish (US)
Article number106385
JournalLeukemia Research
Volume95
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • ADCT-301
  • Acute lymphoblastic leukemia
  • Acute myeloid leukemia
  • Antibody-drug conjugate
  • CD25
  • Camidanlumab tesirine
  • Relapsed/refractory

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study'. Together they form a unique fingerprint.

Cite this