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.


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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.

Reference

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