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Blood. 2018 Jan 25;131(4):387-396. doi: 10.1182/blood-2017-06-789800. Epub 2017 Dec 1.

A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia.

Author information

1
Memorial Sloan-Kettering Cancer Center, New York, NY.
2
Fred Hutchinson Cancer Research Center, Seattle, WA.
3
University of Alabama Birmingham, Birmingham, AL.
4
Massachusetts General Hospital Cancer Center, Boston, MA.
5
Cleveland Clinic, Cleveland, OH.
6
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
7
University of Texas MD Anderson Cancer Center, Houston, TX.
8
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
9
Dana-Farber Cancer Institute, Boston, MA.
10
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
11
Hackensack University Medical Center, Hackensack, NJ.
12
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA.
13
Seattle Genetics, Inc., Bothell, WA; and.
14
City of Hope, Gehr Family Center for Leukemia Research, Duarte, CA.

Abstract

Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5-60 µg/kg) or on days 1 and 4 (20 µg/kg) of 21-day cycles. A total of 131 patients (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or adverse (34%) risk by European LeukemiaNet classification; 50% of patients had underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary embolism and grade 4 hypocellular marrow) occurred during dose finding. Most adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the recommended monotherapy dose of 40 µg/kg, the complete remission + CRi rate was 28% (5 of 18 patients); 50% of patients who responded achieved minimal residual disease negativity. In patients across dose levels who achieved CR or CRi, the median time to full count recovery was 6.4 weeks for neutrophils (≥1000/µL) and 10.6 weeks for platelets (≥100 × 109/L). Vadastuximab talirine demonstrates activity and a tolerable safety profile as a single agent in patients with AML. The recommended monotherapy dose of vadastuximab talirine is 40 µg/kg. This trial was registered at www.clinicaltrials.gov as # NCT01902329.

PMID:
29196412
PMCID:
PMC5813721
DOI:
10.1182/blood-2017-06-789800
[Indexed for MEDLINE]
Free PMC Article

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