Final Results of a Phase 1 Study of Loncastuximab Tesirine in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Mehdi Hamadani, John Radford, Carmelo Carlo-Stella, Paolo F Caimi, Erin G Reid, Owen A O'Connor, Jay Feingold, Kirit M Ardeshna, William M Townsend, Melhem Solh, Leonard T Heffner, David Ungar, Luqiang Wang, Joseph P Boni, Karin Havenith, Yajuan Gu Qin, Brad Kahl

Research output: Contribution to journalArticlepeer-review


The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a Phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and to evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3+3 dose escalation at 15-200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CR). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved CR. Loncastuximab tesirine had good stability in serum, notable anti-tumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for Phase 2 was determined as 150 µg/kg every 3 weeks (Q3W) for 2 doses followed by 75 µg/kg Q3W. Study: NCT02669017.

Original languageEnglish
Pages (from-to)2634-2645
Number of pages12
Issue number19
Publication statusPublished - 13 May 2021

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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