Context: Patients with R/R DLBCL who fail or are ineligible for ASCT have poor outcomes with standard palliative chemotherapy. Epcoritamab is a subcutaneously administered CD3xCD20 bispecific antibody that demonstrated substantial antitumor activity in R/R DLBCL. Objective: Evaluate the safety and efficacy of epcoritamab + GemOx in patients with R/R DLBCL who are ineligible for ASCT in arm 5 of a phase 1/2, open-label trial (EPCORE NHL-2; NCT04663347). Patients: Adults with R/R CD20+ DLBCL who failed or were ineligible for ASCT were included. As of December 1, 2021, 27 patients (median age, 71 y) were treated. Interventions: Patients received subcutaneous epcoritamab (QW, cycle [C] 1–3; Q2W, C4–9; Q4W, C≥10) and GemOx (Q2W, C1–4) until disease progression or unacceptable toxicity (28 d/C). Step-up dosing and prophylactic corticosteroids were required. Results: Of the 27 patients (epcoritamab 24 mg, n=3; 48 mg, n=24), most were stage IV (56%), primary refractory (56%), and/or refractory to last therapy (70%). Median number of prior therapies was 2 (range, 1–13), and median follow-up was 6.0 mo (range, 1.0–11.1), with treatment ongoing in 16 patients (59%). The most common treatment-emergent AEs were CRS (70%), thrombocytopenia (70%), neutropenia (56%), anemia (52%), and infections (52%). CRS events were all grade (G) 1–2, with most cases in C1; all cases resolved. One patient had ICANS (G3). Six patients (22%) had G5 AEs: unrelated to epcoritamab by the investigator in 4 patients; epcoritamab contribution could not be ruled out in 2 patients. The overall response rate for the 25 efficacy-evaluable patients was 92% by PET-CT; 60% had a complete metabolic response (CMR), and 32% had a partial metabolic response (PMR). At data cutoff, the longest duration of response was 6.9 mo. All 3 patients with prior CAR T remained on treatment and in response (2 had CMR and 1 had PMR). Conclusions: In this R/R population with high unmet need, no unexpected safety findings were observed for epcoritamab + GemOx. These initial data are encouraging and warrant further clinical evaluation. Funding: This study was funded by Genmab A/S and AbbVie.
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The TEM analysis was performed at Barcelona University. We thank Dr. Carmen Lopez for her skillful work at the microscope. We are also grateful to Mrs. Eladia Serrano, Mr. Joaquim Villaverde and Mr. G. von Knorring for their expert technical assistance. This work was supported funds from DGICYT (Prog. PB94-0043),
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