Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data.

Lorenzo Falchi Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY info_outline Lorenzo Falchi, Michael Clausen, Fritz Offner, Sven de Vos, Joshua Brody, Kim M. Linton, Sylvia Snauwaert, Raul Cordoba, Jun Wu, Irina Bykhovski, Liwei Wang, Ali Rana, David Belada

Authors Lorenzo Falchi Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY info_outline Lorenzo Falchi, Michael Clausen, Fritz Offner, Sven de Vos, Joshua Brody, Kim M. Linton, Sylvia Snauwaert, Raul Cordoba, Jun Wu, Irina Bykhovski, Liwei Wang, Ali Rana, David Belada Organizations Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, Vejle Hospital, Vejle, Denmark, Universitair Ziekenhuis Gent, Ghent, Belgium, Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA, Icahn School of Medicine at Mount Sinai, New York, NY, The Christie NHS Foundation Trust and Manchester Cancer Research Centre, Manchester, United Kingdom, Department of Hematology, AZ Sint-Jan Hospital, Bruges, Belgium, Fundacion Jimenez Diaz University Hospital, Health Research Institute IIS-FJD, Madrid, Spain, AbbVie Inc., North Chicago, IL, Genmab, Princeton, NJ, 4th Department of Internal Medicine – Hematology, University Hospital and Faculty of Medicine, Hradec Králové, Czech Republic Abstract Disclosures Research Funding Pharmaceutical/Biotech Company This study was funded by Genmab A/S and AbbVie Background: Patients (pts) with 1L diffuse large B-cell lymphoma (DLBCL) typically receive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, around 40% relapse. Complete response rates and long-term outcomes are worse for high-risk pts with International Prognostic Index (IPI) 3–5 or double-hit/triple-hit lymphoma, representing an underserved pt population requiring better curative options. Data from the pivotal study of single-agent epcoritamab, a T-cell–engaging bispecific antibody, demonstrated impressive efficacy and a manageable safety profile (Thieblemont et al, JCO 2022). Preliminary data for epcoritamab + R-CHOP in 1L DLBCL (NCT04663347) showed encouraging efficacy. Here we present results for a larger cohort with longer follow-up. Methods: Pts with 1L CD20 + DLBCL and IPI ≥3 received subcutaneous epcoritamab (cycle [C] 1–4, QW; C5–6, Q3W) + R-CHOP for 6 Cs (21 d each) followed by epcoritamab monotherapy Q4W (28-d Cs) up to a total of 1 y. Results: As of Oct 31, 2022, 47 pts (median age, 64 y) had received epcoritamab 48 mg + R-CHOP with a median follow-up of 11.5 mo (range, 0.8–15.5). All pts had IPI 3–5, 37 (79%) had stage IV disease, and of 25 pts with FISH data available, 11 (44%) had double-hit/triple-hit DLBCL. Median time from diagnosis to first dose was 28 d (range, 3–423). Median dose intensity for R-CHOP was ≥95%. The most common treatment-emergent AEs (TEAEs) of any grade (G) were neutropenia (64%), anemia (62%), CRS (60%), fatigue (40%), pyrexia (40%), injection-site reactions (38%), and nausea (38%). TEAEs led to epcoritamab discontinuation in 3 pts; 1 pt had a G5 TEAE (COVID-19, unrelated to treatment). CRS was predominantly low grade (57% G1–2, 2% G3) and occurred mostly after the first full dose (C1D15); all cases resolved. One pt experienced G2 ICANS, which resolved. All response-evaluable pts (100%) had a response, and 76% had a complete metabolic response (CMR; Table). Notably, response rates were similar for double-hit/triple-hit pts (CMR rate, 82% [9/11]). The median durations of response, progression-free survival, and overall survival were not reached. Responses were durable; at 9 mo, an estimated 96% of pts with CMR remained in CMR. Updated data will be presented. Conclusions: Subcutaneous epcoritamab + R-CHOP induces high CMR rates with a manageable safety profile in pts with 1L high-risk DLBCL, including double-hit/triple-hit pts. These results support the ongoing phase 3 study of epcoritamab + R-CHOP in 1L pts (NCT05578976). Clinical trial information: NCT04663347. Antitumor activity. n (%) Total evaluable n=46 Double-hit/triple-hit n=11 Overall response 46 (100) 11 (100) Complete metabolic response 35 (76) 9 (82) Partial metabolic response 11 (24) 2 (18) Stable/Progressive disease 0 0

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