PROMISING CLINICAL DATA FROM DOSE ESCALATION IN A PHASE IB/II ONGOING STUDY OF MOSUNETUZUMAB WITH POLATUZUMAB VEDOTIN FOR RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN’S LYMPHOMA

Abstract

Introduction: Mosunetuzumab (M) a full-length humanized IgG1 bispecific antibody targeting CD20 and CD3 has shown promising efficacy and safety as monotherapy for relapsed/refractory (R/R) Bcell non-Hodgkin's lymphoma (B-NHL; NCT02500407; Assouline et al. ASH 2020). The combination of M with the anti-CD79b antibody-drug conjugate polatuzumab vedotin (Pola) showed synergistic anti-lymphoma activity in a mouse xenograft model. These data supported a Phase Ib/II open-label multicenter trial of M-Pola for R/R B-NHL (GO40516 NCT03671018). Here we present early clinical data from the Phase Ib cohort. Methods: Patients (pts) with R/R follicular lymphoma (FL grade [Gr] 1-3a) or aggressive NHL (aNHL) including de novo diffuse large B-cell lymphoma (DLBCL) transformed FL (trFL) and FL Gr 3b (FL3b) received Cycle (C) 1 step-up doses of M on Day (D) 1 (1mg) and D8 (2mg) the target dose on C1D15 then continued at the target dose on C2D1 onwards. M was given every 21 days for eight cycles (or 17 cycles if stable disease or a partial response after C8). Pola (1.8mg/ kg) was given with M on D1 of each cycle for six cycles. Results: As of November 17 2020 22 pts had received M-Pola (M target doses: 9mg n = 7; 20mg n = 3; 40mg n = 6; 60mg [with D1 dose of 30mg from C3 onwards] n = 6). Pts had DLBCL (n = 12) FL (n = 3) FL3b (n = 3) and trFL (n = 4). Pt characteristics include: median age of 70 (38-81) years; median of 3 (1-10) prior lines of therapy; 7 (32%) pts had prior CAR-T therapy; 17 (77%) and 19 (86%) pts had disease refractory to last prior therapy and prior anti-CD20 therapy respectively. Median follow-up duration was 9.6 (0.7-23.7) months. The most frequent treatment-related adverse events (AEs) were neutropenia (45.4%) fatigue nausea and diarrhea (all 36.4%). Cytokine release syndrome (CRS) was observed in 2 pts (9.1%; both Gr 1 by ASTCT 2019 criteria). One dose-limiting toxicity (Gr 3 new onset atrial fibrillation) was observed in the 40mg cohort. The maximum tolerated dose was not exceeded. The most common Gr ≥3 and serious AEs were both neutropenia observed in 8 (36.4%) and 3 (13.6%) pts respectively. Two (9.3%) Gr 5 AEs occurred: sudden cardiac death (n = 1) and respiratory failure (n = 1); neither was deemed treatment related. No immune effector cell-associated neurotoxicity was observed. The Table shows preliminary efficacy data. Conclusions: These data indicate that M-Pola has an acceptable safety profile with no Gr ≥2 CRS observed and promising efficacy in pts with R/R NHL with predominantly aggressive disease. The Phase II expansion cohort in R/R DLBCL is ongoing with no mandatory hospitalization required.