GLOFITAMAB PLUS POLATUZUMAB VEDOTIN DEMONSTRATES DURABLE RESPONSES AND A MANAGEABLE SAFETY PROFILE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA

Abstract

Introduction: Glofitamab (Glofit) is a bispecific CD20:CD3 antibody that redirects T cells to eliminate malignant B cells. The CD79b targeted antibody-drug conjugate polatuzumab vedotin (Pola) is approved as combination therapy for the treatment of R/R DLBCL. Glofit and Pola have complementary mechanisms of action with little overlap in toxicity profiles. Data from an open-label, multicenter Phase Ib/II study (NCT03533283) support the manageable safety and encouraging efficacy of Glofit+Pola in R/R DLBCL. We present updated study results. Methods: Patients (pts) received obinutuzumab 1000mg on Day (D) 1 of the first 21-day cycle (C), to mitigate risk of cytokine release syndrome (CRS). Pola 1.8mg/kg was given on C1D2 and D1 of C2-6. Glofit was given with C1 step-up dosing (C1D8 2.5mg; C1D15 10mg; C2-12 D1, 10/30mg) for up to 12 cycles. 24-hour hospitalization was only mandatory after the first Glofit infusion. The primary objective was to establish the recommended Phase II dose of Glofit in combination with Pola (30mg). Additional objectives were safety, efficacy, pharmacokinetics (PK) and biomarkers. Results: As of Jan 25, 2023, 111 pts had received ≥1 dose of study drug; 51% had R/R DLBCL, 24% R/R HGBCL, 23% R/R trFL, and 2% R/R PMBCL. 71% of pts were refractory to their last therapy, median prior therapy lines was 2 (range 1-7, 39% received 1 prior line), and 25% of pts had prior CAR T-cell therapy. Median follow-up was 13.0 months (95% CI: 11.8-16.6). The most common adverse event (AE) was CRS (44%), predominantly of ASTCT Gr 1/2 (30%/14%); one pt had Gr 5 CRS in the context of urosepsis and herpetic stomatitis. Gr 3/4 AEs occurred in 61% of pts, most commonly neutropenia (30%). Glofit-related neurologic AEs occurred in 3 pts and Pola-related peripheral neuropathy was reported in 21% of pts (all Gr 1/2). Serious AE (SAE) were reported in 59% of pts and 9% of pts discontinued therapy due to an AE. Of 109 efficacy-evaluable pts, best ORR (BORR) for both dosing cohorts (per Lugano 2014) was 78%, with best CR (BCR) rate of 56%. Histological BORR and BCR, respectively, were: R/R DLBCL 86% and 61%; R/R trFL 77% and 54%; R/R PMBCL 100% and 100%; HGBCL 60% and 44%. Median PFS was 10.4 months (95% CI: 5.8-19.0) and median DoR was 17.9 months (95% CI: 10.1-NE). Conclusions: Glofit+Pola resulted in frequent and durable responses. The safety profile was consistent and manageable, with mostly low-grade CRS. Updated effi- cacy, PK and biomarker data will be presented.