Final Results of a Phase 1 Study of Loncastuximab Tesirine in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
On May 13, 2021 in the journal Blood, investigators report on the final results of the phase 1 clinical trial of loncastuximab tesirine (LT) in relapsed refractory B-cell non-Hodgkin’s lymphoma. LT is an antibody drug conjugate, comprising of a humanized anti-CD19 monoclonal antibody, conjugated to a pyrrolobenzodiazepine dimer toxin. The authors report on the final results of the phase 1 clinical trial. Objectives included a maximum tolerated dose and recommended doses for expansion and safety evaluation as well as clinical activity, pharmacokinetics and immunogenicity of LT.
Of the 183 patients who received the antibody drug conjugate, with 3+3 dose escalation at 15-200 mcg/kg and dose expansion at 120-150 mcg/kg, dose-limiting toxicities were seen in 4 patients. The maximum tolerated dose had not been reached. While cumulative toxicity was higher at 200 mcg/kg. Hematologic adverse events were very common. This was followed closely by fatigue, nausea, edema and LFT elevation. The overall response rate in patients who were valuable was 45.6%, including 26.7% complete responses. Overall response rates in patients with diffuse large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma were 42.3, 46.7 and 70.6%, respectively. The median duration of response in all patients was 5.4 months. It was not reached in DLBCL patients at doses above 120 mcg/kg and who had achieved a complete response. The antibody drug conjugate had good stability in serum per the investigators. There was also notable antitumor activity and an acceptable safety profile.
The authors recommended continuing studies in B-cell lymphomas and a recommended dose for phase 2 was determined as 150 mcg/kg every 3 weeks for 2 doses followed by 75 mcg/kg every 3 weeks”