Faculty Collaboration Database

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res 2019 Dec 01;25(23):6986-6994

Date

11/07/2019

Pubmed ID

31685491

DOI

10.1158/1078-0432.CCR-19-0711

Scopus ID

2-s2.0-85075960499 (requires institutional sign-in at Scopus site)   71 Citations

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).

PATIENTS AND METHODS: 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.

Author List

Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antigens, CD19
Antineoplastic Agents
Benzodiazepines
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Humans
Immunoconjugates
Lymphoma, B-Cell
Male
Middle Aged
Neoplasm Recurrence, Local
Prognosis
Pyrroles
Salvage Therapy
Survival Rate
Young Adult