Results from the Epcore NHL-2 Trial Arm 8: Epcoritamab SC + R-Mini-CHOP Leads to High Complete Metabolic Response Rates in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma Ineligible for Full-Dose R-CHOP

Background Low-dose rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) is standard treatment (tx) for patients (pts) with previously untreated (1L) diffuse large B-cell lymphoma (DLBCL) who cannot receive full-dose R-CHOP due to age, frailty, or comorbidities; however, outcomes are suboptimal. Epcoritamab, a subcutaneous (SC) CD3xCD20 bispecific antibody, is approved in the US, Europe, and Japan. In the US, it is approved for the tx of adults with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic tx. In the 1L setting, epcoritamab SC had a favorable safety profile and promising efficacy in pts with high-risk DLBCL. We report initial data from arm 8 of the phase 1/2 EPCORE™ NHL-2 study (NCT04663347) evaluating epcoritamab SC + R-mini-CHOP in 1L DLBCL. Methods Adult pts with 1L CD20+ DLBCL who were not considered candidates for full-dose R-CHOP (age ≥75 y or age ≥65 y with comorbidities) were enrolled. Pts received epcoritamab SC (QW, cycle [C] 1–2 [21 d each]; Q3W, C3–6 [21 d each]; Q4W, C7–8 [28 d each]) with R-mini-CHOP in C1–6 (Q3W). A safety run-in was conducted. Primary endpoint was overall response rate (ORR) assessed by PET-CT per Lugano criteria. Results As of Apr 24, 2023, 28 pts (median age, 81 y) had received epcoritamab SC 48 mg + R-mini-CHOP; 14 pts (50%) had International Prognostic Index 3–5, 10 pts (36%) had bulky disease (>6 cm), and 15 pts (54%) had stage IV disease. Median follow-up was 6.2 mo (range, 2.5+ to 11.7); 9 pts (32%) completed tx and 15 pts (54%) were still on tx. R-mini-CHOP median relative dose intensity was ≥94%. There were no dose-limiting toxicities. The most common tx-emergent AEs (TEAEs) of any grade (G) were cytokine release syndrome (CRS) (43%), neutropenia (32%), fatigue (25%), anemia (21%), constipation (21%), and hypokalemia (21%). TEAEs decreased over time; 3 pts (11%) discontinued tx due to TEAEs. One G5 TEAE (cytomegalovirus infection reactivation) was reported. Most CRS events were low grade (G1–2: 39%, G3: 4%, G≥4: 0%), had predictable timing, and were observed after the first full dose (C1D15). All CRS events resolved (median time to resolution, 3 d [range, 1–7]). There were no ICANS events. Among 20 efficacy-evaluable pts, ORR was 100%, with 17 pts (85%) achieving complete metabolic response (CMR). Median time to response was 1.4 mo (Figure). At both 6 and 9 mo, most complete responders remained in CMR, suggesting durability of response. Updated results will be presented. Conclusions Epcoritamab SC + R-mini-CHOP showed encouraging efficacy with high response rates in pts with 1L DLBCL ineligible for full-dose R-CHOP, including elderly, frail, and high-risk pts. Findings were consistent with previous data, with no new safety signals, supporting further investigation of epcoritamab-based therapies in 1L DLBCL.