Loncastuximab tesirine, an antibody-drug conjugate for relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), warrants continued study at a maximum dose of 150 µg/kg, according to results of a phase 1 study published in Blood.
R/R B-NHL carries a poor prognosis with salvage chemotherapy, creating a need for new therapies. Loncastuximab tesirine showed promising antitumor activity in preclinical studies, and a first in-human dose escalation study found an acceptable safety profile.
This phase 1, 2-part, open-label study included 183 total patients with confirmed R/R B-NHL. A total of 139 patients had diffuse large B-cell lymphoma (DLBCL), 15 had mantle cell lymphoma, 14 had follicular lymphoma, and 15 had other type of B-NHL.
Patients in part 1 received doses ranging from 15 to 200 µg/kg. During part 2 of the study (dose expansion), patients received doses of 120 µg/kg or 150 µg/kg every 3 weeks.
A total of 83 patients discontinued treatment because of progressive disease and 111 patients died during the trial period.
There were 4 patients who had dose-limiting toxicities (DLTs) during part 1. A total of 98.9% of patients had at least 1 treatment-emergent adverse event (TEAE), most commonly hematologic TEAEs or fatigue. There were 141 patients who had grade 3 or greater TEAEs.
The overall response rate (ORR) of 180 evaluable patients was 45.6%, with 48 complete remissions and 34 partial remissions. Patients who received a higher dose of the study drug had higher response rates. The median progression-free survival (PFS) for all patients was 3.1 months.
In part 2, dexamethasone premedication reduced the incidence of edema and effusion, and this approach is recommended to avoid pyrrolobenzodiazepine (PBD)-related toxicities.
The study authors concluded that the recommended dose for loncastuximab tesirine for a phase 2 trial is 150 µg/kg every 3 weeks for 2 doses, followed by 75 µg/kg every 3 weeks for subsequent doses.
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Hamadani M, Radford J, Carlo-Stella C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021;137(19):2634-2645. doi:10.1182/blood.2020007512