High Complete Metabolic Response Rates with Epcoritamab SC + GemOx in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Ineligible for Autologous Stem Cell Transplant: Updated Results from Epcore NHL-2

Background Novel, effective treatment (tx) options are needed for patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who fail or are ineligible for autologous stem cell transplant (ASCT). Subcutaneous (SC) epcoritamab, a CD3xCD20 bispecific antibody, demonstrated deep, durable responses with a manageable safety profile as monotherapy in R/R DLBCL. Epcoritamab SC is approved in the US, Europe, and Japan. In the US, it is approved for adults with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma, after ≥2 lines of systemic tx. We present updated results from the EPCORE™ NHL-2 phase 1/2 trial (NCT04663347). Methods Adults with R/R CD20+ DLBCL who failed or were ineligible for ASCT were enrolled and received epcoritamab SC in 28-d cycles (C): QW, C1–3; Q2W, C4–9; Q4W, C≥10 until progressive disease or unacceptable toxicity. Pts received GemOx Q2W in C1–4. Step-up epcoritamab dosing (2 step-up doses followed by 48-mg full doses) and corticosteroid prophylaxis were required in C1 to mitigate cytokine release syndrome (CRS). The primary endpoint was overall response rate (ORR) by PET-CT per Lugano criteria. Results On or before Aug 24, 2022, 34 pts (median age, 71 y; range, 47–87) received epcoritamab SC 48 mg + GemOx. At the data cutoff date (Apr 24, 2023; median [range] follow-up, 20.3 mo [1.0+‒26.8]), tx was ongoing in 35% of pts. Most pts (68%) had stage III or IV disease, 53% had primary refractory disease, and 38% were refractory to ≥2 consecutive lines of prior tx. Median prior tx lines was 2 (range, 1–6); 7 pts (21%) had prior chimeric antigen receptor T-cell therapy (CAR T), and 5 pts (15%) had prior ASCT. The ORR was 91% (31/34); 59% (20/34) had complete metabolic response (CMR). Median times to response and CMR were 1.5 mo and 2.6 mo, respectively. The ORR/CMR rates were 94%/39% in pts with primary refractory disease, 89%/78% in pts ≥75 y of age, and 90%/50% in pts with International Prognostic Index ≥3 (Table). Response was comparable for pts with (ORR 86%; CMR rate 57%) and without (ORR 93%; CMR rate 59%) prior CAR T. The most common tx-emergent adverse events of any grade (G) were thrombocytopenia/decreased platelet count (68%), diarrhea (59%), anemia (56%), CRS (56%), and neutropenia/decreased neutrophil count (56%). Most CRS events were low grade (53% G1–2; 3% G3) and primarily occurred following the first full dose (C1D15); all events resolved and none resulted in epcoritamab discontinuation. COVID-19 was reported in 32% of pts. Conclusions Epcoritamab SC + GemOx led to high CMR rates in this difficult-to-treat R/R DLBCL ASCT-ineligible population. The safety profile was consistent with those of the individual drugs, with no new safety signals.