First data from phase 1b/2 EPCORE NHL-4: Epcoritamab (Epcor) in Chinese patients (Pts) with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

Abstract

e19001 Background: DLBCL comprises 38% of all non-Hodgkin lymphoma (NHL) in China. Outcomes for R/R DLBCL remain poor despite treatment (tx) advances including CAR T-cell therapy, for which access can be limited. Thus, an unmet need in China remains, especially for chemorefractory R/R DLBCL. Subcutaneous (SC) epcor is a CD3xCD20 bispecific antibody approved globally, including the US, for R/R DLBCL and follicular lymphoma (FL). Here we present first efficacy and safety data from R/R DLBCL Chinese pts treated with epcor monotherapy in the pivotal EPCORE NHL-4 (NCT5201248) trial. Methods: Pts had R/R NHL with ≥2 lines of prior systemic tx and were administered 48 mg epcor SC in 28-day cycles (C): QW, C1-3; Q2W, C4-9; Q4W, C10+ until disease progression or unacceptable toxicity. In C1, step-up dosing (day [D] 1, 0.16 mg; D8, 0.8 mg; D15, D22, 48 mg) and prophylactic corticosteroids were used to prevent cytokine release syndrome (CRS). Key endpoints included tx-emergent adverse events (TEAEs), response rates (overall response rate [ORR]/complete response rate [CRR]) and progression-free survival (PFS) by independent review committee (IRC), and duration of response (DoR/DoCR) by IRC. Results: As of June 19, 2024, 42 pts were enrolled (3 DLBCL, 2 FL in safety run-in; 37 DLBCL in dose expansion). In dose expansion, median age was 57.0 y and pts received ≥1 epcor dose; median follow-up was 18.5 mo. In dose expansion, 73% of pts had advanced disease (Ann Arbor Stage III–IV), 89% had primary refractory disease, and 65% were refractory to the last line of anti-CD20 tx. Median prior lines of tx was 3 (range, 2–7). Most pts (97%) had ≥1 Grade (G) 3/4 TEAE, most commonly lymphopenia (89%), neutropenia (57%), leukopenia (35%), and thrombocytopenia (22%). CRS was reported in 84% of pts: G1 51%, G2 32%, and no G≥3. Most CRS events occurred after the first full dose (C1D15), with median time to onset of 16 D (range, 2–29). All CRS events resolved and no pts discontinued epcor due to CRS. No pts had immune effector cell-associated neurotoxicity syndrome, and 1 pt (3%) had G3 clinical tumor lysis syndrome that resolved without dose interruption. Three fatal TEAEs were all due to progressive disease and unrelated to epcor. ORR was 65% and CRR was 38%; median DoR, DoCR, and OS were not reached (NR; Table). Conclusions: Epcor monotherapy showed favorable outcomes in Chinese pts with refractory and heavily pretreated R/R DLBCL.High ORR and CRR were achieved early and safety was manageable. CRS was low grade with predictable timing. Our results are consistent with the pivotal EPCORE NHL-1 and NHL-3 trials and support further development of epcor in China. Clinical trial information: NCT05201248 . Efficacy by IRC. Dose Expansion (n=37) ORR, % 64.9 CR 37.8 PR 27.0 Median time to response, mo (range) 1.4 (1.1–2.8) Time to CR 2.2 (1.1–5.4) Median DoR, mo (95% CI) NR (1.5–NR) DoCR NR (3.9–NR) Median PFS, mo (95% CI) 4.5 (2.7–NR) Median OS, mo (95% CI) NR (6.5–NR)