Subcutaneous (SC) Epcoritamab (GEN3013; DuoBody-CD3xCD20) in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL): Dose-Escalation Data from a Phase I/II Trial

Context: CD3×CD20 bispecific antibodies (bsAbs) have demonstrated promising results in R/R B-NHL. Epcoritamab is a novel subcutaneously-administered bsAb with a favorable safety profile and encouraging preliminary anti-tumor activity in both aggressive and indolent B-NHL in a Phase I/II trial ( NCT03625037 ). Objective: Determine recommended phase 2 dose, safety, and anti-tumor activity of epcoritamab. Participants: Adults with R/R CD20+ B-NHL. Intervention: SC 1 mL injection of flat-dose epcoritamab (dosing escalation range 0.0128–48 mg preceded by a priming and intermediate dose) administered in 28-day cycles until disease progression or unacceptable toxicity. Results: As of 24 April 2020, 58 patients with a median (range) age 68 (21–84) years were enrolled. Most patients had DLBCL (67.2%) or FL (19.0%) and received a median (range) of 3 (1–6) and 5 (1–18) prior lines of treatment, respectively. No dose-limiting toxicities were observed (median follow-up [range]: 2.7 [0.2–16.4] months). MTD has not been reached. Majority of TEAEs were mild (Grade 1–2); the most common TEAEs (\u003e35%) were pyrexia (69.0%), fatigue (41.4%), and injection site reaction (41.4%; all Grade 1). AEs of special interest included CRS (56.9%; no Grade ≥3 events occurred; all resolved) and neurotoxicity (6.9%; median [range] duration of events: 1 [ Conclusions: The safety, efficacy, and pharmacokinetics data support epcoritamab 48 mg SC (1 mL, single dose) to be explored in the expansion phase. SC epcoritamab continues to demonstrate a favorable safety profile consistent with previous reported data. Notably, there were no treatment-related deaths, no febrile neutropenia, tumor lysis syndrome, or Grade ≥3 CRS events. Epcoritamab has the potential for outpatient administration. Epcoritamab induces rapid, deep responses in heavily pretreated patients across different B-NHL subtypes. Funding: Genmab A/S.