Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study Journal Article
| Authors: | Goldberg, A. D.; Atallah, E.; Rizzieri, D.; Walter, R. B.; Chung, K. Y.; Spira, A.; Stock, W.; Tallman, M. S.; Cruz, H. G.; Boni, J.; Havenith, K. E. G.; Chao, G.; Feingold, J. M.; Wuerthner, J.; Solh, M. |
| Article Title: | Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study |
| 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. © 2020 Elsevier Ltd |
| Keywords: | adult; clinical article; aged; middle aged; allogeneic stem cell transplantation; constipation; drug tolerability; fatigue; neutropenia; paresthesia; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; hypophosphatemia; monotherapy; side effect; united states; cytarabine; multiple cycle treatment; pharmacodynamics; anemia; nausea; thrombocytopenia; vomiting; qt prolongation; acute lymphoblastic leukemia; abdominal pain; asthenia; drug dose escalation; dyspnea; febrile neutropenia; fever; hyperglycemia; lymphocytopenia; pneumonia; rash; heart palpitation; hyperkalemia; hypoalbuminemia; maculopapular rash; multicenter study; immunogenicity; daunorubicin; muscle weakness; peripheral edema; drug clearance; open study; phase 1 clinical trial; drug half life; autoimmune disease; gamma glutamyltransferase; dry skin; neurologic disease; interleukin 2 receptor alpha; hypocalcemia; blast cell; cd25; decreased appetite; relapsed/refractory; hypertransaminasemia; acute myeloid leukemia; contusion; leukocytoclastic vasculitis; antibody-drug conjugate; infusion related reaction; human; male; female; priority journal; article; ixazomib; adct-301; camidanlumab tesirine |
| Journal Title: | Leukemia Research |
| Volume: | 95 |
| ISSN: | 0145-2126 |
| Publisher: | Elsevier Ltd |
| Date Published: | 2020-08-01 |
| Start Page: | 106385 |
| Language: | English |
| DOI: | 10.1016/j.leukres.2020.106385 |
| PUBMED: | 32521310 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2020 -- Source: Scopus |
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