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

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Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid EG, O'Connor OA, Feingold J, Ardeshna KM, Townsend WM, Solh M, Heffner LT, Ungar D, Wang L, Boni JP, Havenith K, Qin YG, Kahl B

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

Blood. 2020 Nov 19. pii: 474210. doi: 10.1182/blood.2020007512.

PubMed ID
33211842 [ View in PubMed
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Abstract

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 microg/kg and dose expansion at 120 and 150 microg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 microg/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 microg/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 microg/kg every 3 weeks (Q3W) for 2 doses followed by 75 microg/kg Q3W. Study: NCT02669017.

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