CLINICAL ACTIVITY OF REGN1979, AN ANTI‐CD20 X ANTI‐CD3 BISPECIFIC ANTIBODY (AB) IN PATIENTS (PTS) WITH (W/) RELAPSED/REFRACTORY (R/R) B‐CELL NON‐HODGKIN LYMPHOMA (B‐NHL) (2019)

Introduction: REGN1979 (R1979) is an anti-CD20 x anti-CD3 bispecific IgG4 Ab. We report updated results of a Phase 1 trial of R1979 in pts w/ R/R B-NHL previously treated w/ anti-CD20 Ab therapy. Primary objectives are to determine safety, tolerability, and occurrence of dose limiting toxicities (DLTs). Other objectives are to assess antitumor activity, pharmacokinetics (PK), and pharmacodynamics. Methods: Eligible pts w/ R/R B-NHL must have received ≥1 prior CD20-directed Ab therapy. Treatment (tx) consists of 12 weekly intravenous doses of R1979 followed by every 2-week dosing for 12 doses (total of 36 weeks). Results: As of Dec 6, 2018, 71 pts (diffuse large cell B-cell lymphoma [DLBCL] [n=39], follicular lymphoma [FL] grade [Gr] 1-3a [n=17], other [mantle cell lymphoma {MCL}, marginal zone lymphoma {MZL}, FL grade 3b, FL unknown/ungraded, or Waldenstrom macroglobulinemia {WM} [n=15]) were treated w/ R1979 0.03–80 mg and received a median of 9 doses (range 1–24). Ten pts remain on tx; 15 completed tx; 46 discontinued early (29 due to progressive disease [PD]). No pts w/ B-NHL experienced a DLT. Most common tx-emergent adverse events (AEs) were pyrexia (n=56), chills (n=38), cytokine release syndrome (CRS; n=37, w/4 experiencing Gr ≥3). The severity of CRS symptoms declined through optimized pre-medication even w/ R1979 dose escalation. Most common Gr ≥3 AEs were decreased neutrophils/neutropenia (n=14), decreased lymphocytes/lymphopenia (n=14), anemia (n=12). No seizure and/or encephalopathy was reported. No neurological event required tx termination. Four pts discontinued due to AEs: Gr 3 hemolysis; Gr 3 fatigue; Gr 3 pneumonia; and Gr 3 neck abscess (1 each). Nine pts died on study: PD (n=6), gastric perforation (n=1), cardiac arrest (n=1), lung infection (n=1). Tx w/ R1979 at doses ≥5 mg has shown marked efficacy in R/R FL Gr 1–3a (ORR: 100% [10/10 OR; 8/10 CR; 2/10 PR]), while increasing efficacy is observed in pts w/ R/R DLBCL (and other B-NHL subtypes) as the dose is further increased (Table and Figure); of note, in patients with R/R DLBCL, 2/11 (18%) had responses at doses between 5-12 mg, 6/11 (55%) had responses at doses between 18-40 mg, and 2/2 (100%) had responses at the 80 mg dose, with both of these latter being CRs. Elevated levels of serum cytokines were observed w/ dosing; however, no correlation was observed w/ clinical efficacy. Immunohistological analysis of malignant lymph node tissue demonstrated that pts w/ high and low CD20 achieved clinical response. Relapse among responders was seen w/ either maintenance or loss of CD20 expression, suggesting antigen-dependent and independent disease escape mechanisms. Keywords: CD20; CD3; non-Hodgkin lymphoma (NHL). Disclosures: Topp, M: Research Funding: Regeneron Pharmaceuticals, Inc. Arnason, J: Research Funding: Regeneron Pharmaceuticals, Inc. Advani, R: Research Funding: Regeneron Pharmaceuticals, Inc. Brown, J: Research Funding: Regeneron Pharmaceuticals, Inc. Allan, J: Research Funding: Regeneron Pharmaceuticals, Inc. Ansell, S: Research Funding: Regeneron Pharmaceuticals, Inc. O'Brien, S: Research Funding: Regeneron Pharmaceuticals, Inc. Chavez, J: Research Funding: Regeneron Pharmaceuticals, Inc. Duell, J: Research Funding: Regeneron Pharmaceuticals, Inc. Rosenwald, A: Research Funding: Regeneron Pharmaceuticals, Inc. Charnas, R: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Ambati, S: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Adriaens, L: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Ufkin, M: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Zhu, M: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Li, J: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Gasparini, P: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Jankovic, V: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Fiaschi, N: Employment Leadership Position: Regeneron Pharmaceuticals, Inc.. Zhang, W: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Hamon, S: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Thurston, G: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Murphy, A: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Yancopoulos, G: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Lowy, I: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Sternberg, D: Employment Leadership Position: Regeneron Pharmaceuticals, Inc. Bannerji, R: Research Funding: Regeneron Pharmaceuticals, Inc.