According to findings of a first-in-human study published in the Journal of Clinical Oncology, single-agent mosunetuzumab, administered with step-up dosing, demonstrated a manageable safety profile and induced durable complete responses (CR) in patients with aggressive and indolent relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).
The researchers reported initial results of a phase 1 dose-escalation study evaluating safety, tolerability, and efficacy of the CD20/CD3-targeting bispecific antibody mosunetuzumab in patients with R/R B-NHLs (ClinicalTrials.gov identifier: NCT02500407).
The investigators administered single-agent mosunetuzumab to eligible patients (older than 18 years with histologically confirmed R/R B-NHL expected to express CD20 and no available therapy expected to improve survival) intravenously in 3-week cycles, at a fixed dose (8 dose cohorts with 1-8 patients/dose; 0.05-2.8 mg; cycle 1 day 1) or with ascending (step-up) doses (11 dose-escalation cohorts with 1-10 patients/dose; 0.4/1.0/2.8-1.0/2.0/60 mg; cycle 1 days 1, 8, and 15), for 8 or 17 cycles depending on tumor response. Maximum tolerated dose was not exceeded with either dosing schedule. Findings from the dose escalation were reported.
Of the 233 patients enrolled in the study, 197 were in the ascending-dose group (65% aggressive B-NHL and 34.5% indolent B-NHL). The median age of ascending-dose patients was 61 years (range, 19-91). The group had received a median of 3 prior systemic therapies (range, 1-14), with 75.6% refractory to their last treatment, and 9.6% had received prior CAR-T therapy.
The median treatment duration was 4.0 months (range, 0.3-12.1), and patients received a median of 5 cycles (range, 1-17). The median duration of response (DOR) follow up was 11.9 months (95% CI, 9.3-13.8).
Among the ascending-dose group, common adverse events (AEs; ≥ 20% of patients) were neutropenia (28.4%; grade ≥3, 25.4%), cytokine release syndrome (27.4%; grade ≥3, 1.0%), hypophosphatemia (23.4%; grade ≥3, 15.2%), fatigue (22.8%), and diarrhea (21.8%). Treatment discontinuation due to AEs was reported in 3.6% of patients. Grade 5 AEs unrelated to disease progression occurred in 3 patients in the ascending-dose group (and 1 patient in the fixed-dose group), of which 2 were related to treatment (1patient with chronic active Epstein-Barr virus infection died of hemophagocytic lymphohistiocytosis and 1patient died of pneumonia).
Among the ascending-dose group, best overall response rates was 34.9% in patients with aggressive B-NHL and 66.2% in patients with indolent B-NHL; CR rates were 19.4% and 48.5%, respectively. Among patients with CR, the median DOR was 22.8 months (95% CI, 7.6-not estimable [NE]) and 20.4 (95% CI, 16-NE) in patients with aggressive and indolent B-NHL, respectively.
The recommended phase 2 dose (1/2/60/60/30 mg) is under further evaluation in the expansion phase of the study.
Disclosure: This research was supported by Genentech, Inc.. Please see the original reference for a full list of disclosures.
Budde LE, Assouline S, Sehn LH, et al. Single-agent mosunetuzumab shows durable complete responses in patients with relapsed or refractory B-cell lymphomas: phase I dose-escalation study. J Clin Oncol. 2022;40(5):481-491. doi:10.1200/JCO.21.00931