Subcutaneous (SC) epcoritamab induces complete responses across R/R B-cell NHL subtypes: Updated dose-escalation data

Abstract

Background: Epcoritamab is a CD3CD20 bispecific antibody with a favorable safety profile and encouraging preliminary antitumor activity in both aggressive and indolent B-NHL in a phase I/II trial (NCT03625037). Updated dose-escalation data are reported here. Methods: Adults with R/R CD20+ B-NHL receive a SC 1 mL injection of flat-dose epcoritamab in 28-day cycles (q1w: cycles 1-2; q2w: cycles 3-6; q4w thereafter) until disease progression or unacceptable toxicity. Objectives include safety and antitumor activity. Results: As of 6 July 2020, 67 patients (pts) were enrolled (DLBCL, 67%; FL, 18%; MCL, 6%). Pts were heavily pretreated, with a median (range) of 3.0 (1-6) prior lines of therapy for DLBCL and 4.5 (1-18) for FL. A total of 6 pts received prior CAR-T therapy. At median follow-up of 8.3 months, treatment is ongoing in 25 pts (37%). Epcoritamab was generally well tolerated, with no discontinuations due to treatment-emergent adverse events (TEAEs). The most common TEAEs were pyrexia (70%), local injection-site reactions (48%), and fatigue (45%). Observed TEAEs of special interest were cytokine release syndrome (CRS; all events were Gr 1/2 [58%], no Gr 3/4) and limited neurotoxicities (Gr 1, 3%; Gr 3, 3%; all transient). There were no DLTs, febrile neutropenia events, or deaths due to TEAEs. In pts with DLBCL treated with epcoritamab 12 mg (n¼18), ORR was 66.7% (6 CR). For pts who received higher doses (48 mg [RP2D], n¼4; 60 mg, n¼3) ORR was 100% (2 CR, 5 PR). All 4 DLBCL pts with prior CAR-T therapy achieved a response (2 CR, 2 PR). In FL (epcoritamab 0.76 mg, n¼8), ORR was 100% (2 CR). Responses (1 CR,1 PR) were observed in 2/4 pts with blastoid variant MCL. Conclusions: Epcoritamab demonstrates a consistent, favorable safety profile, with no Gr 3 CRS events and limited neurotoxicity, in support of future outpatient administration. Emerging data are encouraging, including CR in heavily y pretreated pts with DLBCL, FL, and MCL.