ABCL-351: Promising Tolerability and Efficacy Results from Dose-Escalation in an Ongoing Phase Ib/II Study of Mosunetuzumab with Polatuzumab Vedotin (Pola) in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL)

Abstract

<h3>Context</h3> Mosunetuzumab (Mosun), a full-length, humanized, IgG1 CD20xCD3 bispecific antibody, showed promising efficacy/safety for R/R B-NHL (NCT02500407; Assouline, <i>et al.</i> ASH 2020). Mosun combined with the anti-CD79b antibody-drug conjugate Pola showed synergistic anti-lymphoma activity in a mouse xenograft model, supporting the Phase Ib/II, open-label, multicenter trial of Mosun-Pola for R/R B-NHL (GO40516, NCT03671018). <h3>Objective</h3> To present early clinical data from the Phase Ib cohort of GO40516. <h3>Methods</h3> Patients with R/R follicular lymphoma (FL, grade 1–3a) or aggressive NHL (aNHL), including <i>de novo</i> diffuse large B-cell lymphoma (DLBCL), transformed FL (trFL), and grade 3b FL (FL3b), received Cycle (C)1 step-up doses of Mosun on Day (D)1 (1 mg) and D8 (2 mg), and target dose on C1D15, continuing from C2D1. Mosun was given every 21 days for eight cycles, continuing for ≤17 cycles. Pola (1.8 mg/kg) was administered with Mosun on D1 of six cycles. <h3>Results</h3> As of November 17, 2020, 22 patients received Mosun-Pola (Mosun target doses: 9 mg, n=7; 20 mg, n=3; 40 mg, n=6; 60 mg [D1 dose 30 mg from C3 onward], n=6). Patients had DLBCL (n=12), FL (n=3), FL3b (n=3), and trFL (n=4). Median age: 70 (38–81) years; median 3 (1–10) prior lines of therapy; prior chimeric antigen receptor T-cell (CAR-T) therapy (n=7; 32%). Median follow-up duration: 9.6 (0.7–23.7) months. Most frequent treatment-related adverse events (AEs): neutropenia (45.4%), fatigue, nausea, and diarrhea (all 36.4%). Cytokine release syndrome was observed in two patients (9.1%; both grade 1 [Lee, <i>et al.</i> Biol Blood Marrow Transplant 2019]). One dose-limiting toxicity (grade 3 new-onset atrial fibrillation) was observed in the 40 mg cohort; maximum tolerated dose not exceeded. Most common grade ≥3 AE: neutropenia (n=8; 36.4%). Two (9.3%) grade 5 AEs occurred (sudden cardiac death [n=1]); respiratory failure [n=1]); neither was deemed treatment-related. Complete responses were achieved with Mosun-Pola in patients with R/R aNHL (n=9; 47.4%), prior CAR-T therapy (n=2; 28.6%) and FL (n=3; 100%). <h3>Conclusions</h3> These data indicate that Mosun-Pola has an acceptable safety profile and shows promising efficacy in patients with predominantly aggressive R/R NHL. The Phase II expansion cohort in patients with R/R DLBCL is ongoing, with no requirement for mandatory hospitalization.