An ongoing phase 1/1b trial investigating novel treatment regimens with mosunetuzumab in relapsed/refractory B-cell nonhodgkin lymphoma.

Abstract

Background: Mosunetuzumab is a novel CD20/CD3 bispecific antibody that directs T-cells to engage and eliminate malignant B-cells. Interim results from an ongoing, open-label, multicentre, phase 1/1b study (NCT02500407; GO29781) indicate that mosunetuzumab monotherapy administered intravenously (IV) induces durable complete responses with favourable safety in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) (Budde et al. ASH 2018). We report details of 2 other ongoing dose-escalation groups from this study: Group D assesses mosunetuzumab administered subcutaneously (SC) as an approach intended to minimize cytokine-driven toxicities; Group E combines mosunetuzumab and atezolizumab for potentially enhanced clinical efficacy with the addition of immune checkpoint blockade. Dose-expansion cohorts in patients with R/R diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (tFL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) are ongoing. Method(s): Patients with R/R NHL (age >=18 years; ECOG performance status of 0 or 1) in Group D receive a fixed dose of mosunetuzumab SC on Day 1 of each 21-day cycle, up to a maximum of 17 cycles; patients in Group E receive ascending doses of mosunetuzumab IV on Day 1, Day 8 and Day 15 of Cycle 1 (step-up dosing), then from Cycle 2 onwards, a fixed dose on Day 1 of every 21-day cycle with concurrent administration of atezolizumab (1200 mg IV), up to a maximum of 17 cycles. Primary outcome measures are maximum tolerated dose (MTD) based on dose-limiting toxicities, tolerability, pharmacokinetics and best objective response. Dose-expansion cohorts are enrolling patients with R/R DLBCL/tFL, FL, or MCL and patients will receive doses of mosunetuzumab up to the MTD. Details of patient enrolment for the dose-escalation and dose-expansion cohorts are provided (Table).