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Clin Cancer Res. 2019 Nov 4. doi: 10.1158/1078-0432.CCR-19-0711. [Epub ahead of print]

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma.

Author information

1
Department of Medicine, Oncology Division, Washington University, St. Louis, Missouri. bkahl@wustl.edu.
2
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
3
NIHR Experimental Cancer Medicine Centre, The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom.
4
Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas University, Milan, Italy.
5
Case Western Reserve, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
6
Division of Hematology/Oncology, University of California San Diego Moores Cancer Center, La Jolla, California.
7
ADC Therapeutics America Inc., Murray Hill, New Jersey.
8
Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
9
Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
10
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
11
ADC Therapeutics (UK) Limited, London, United Kingdom.
12
Center for Lymphoid Malignancies, Columbia University Medical Center, The New York Presbyterian Hospital, New York, New York.

Abstract

PURPOSE:

ADCT-402 (loncastuximab tesirine) is an antibody-drug conjugate comprising a CD19-targeting antibody and pyrrolobenzodiazepine dimers. A first-in-human study evaluated the safety and preliminary clinical activity of loncastuximab tesirine in patients with B-cell non-Hodgkin lymphoma (NHL).

EXPERIMENTAL DESIGN:

A multicenter, phase I, dose-escalation and dose-expansion study enrolled patients ages ≥18 years with relapsed/refractory (R/R) B-cell NHL. Patients received loncastuximab tesirine every 3 weeks at doses assigned by a 3+3 dose-escalation design. Dose escalation was used to assess the safety and tolerability of loncastuximab tesirine to determine the dose for expansion. Secondary objectives evaluated clinical activity, characterized the pharmacokinetic profile, and evaluated antidrug antibodies.

RESULTS:

During dose escalation, 88 patients with R/R B-cell NHL were treated with loncastuximab tesirine at doses 15 to 200 μg/kg. Treatment-emergent adverse events (TEAEs) were experienced by 87/88 (98.9%) patients. Most common TEAEs (≥20% of patients) were hematologic abnormalities, fatigue, edema, liver test abnormalities, nausea, rash, and dyspnea. Grade ≥3 TEAEs (≥5% of patients) included hematologic abnormalities, liver test abnormalities, fatigue, and dyspnea. Overall response rate at doses ≥120 μg/kg was 59.4% (41 of 69 patients; 40.6% complete response; 18.8% partial response). Median duration of response, progression-free survival, and overall survival (all doses) were 4.8, 5.5, and 11.6 months, respectively. Drug exposure increased with increasing dose, showing moderate accumulation with multiple doses ≥150 μg/kg. There was no evidence of immunogenicity.

CONCLUSIONS:

Loncastuximab tesirine had promising activity with acceptable safety in this dose-escalation study. A phase II study with initial dosing at 150 μg/kg has been initiated based on these results.

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