P1135: SUBCUTANEOUS EPCORITAMAB IN COMBINATION WITH RITXUIMAB + LENALIDOMIDE IN RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA: PHASE 1/2 TRIAL UPDATE

Background: Patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL) experience less frequent and shorter responses with each line of treatment. Although the rituximab + lenalidomide (R2) regimen is effective and has an acceptable safety profile in R/R FL, FL remains incurable; therefore, better treatment options are needed to help pts achieve durable responses. Epcoritamab is a subcutaneously administered bispecific antibody that binds to CD3 on T cells and CD20 on malignant B cells. In the dose-escalation portion of the first-in-human phase 1/2 trial (EPCORE NHL-1), epcoritamab monotherapy (0.76–48 mg) resulted in an overall response rate (ORR) of 90% and a complete response rate of 50% in pts with R/R FL. Because epcoritamab and R2 have distinct mechanisms of action and generally non-overlapping toxicity profiles, combining these treatments may safely enhance antitumor response. Aims: To present updated results for epcoritamab with R2 in pts with R/R FL (EPCORE NHL-2 arm 2; NCT04663347). Methods: Adult pts with R/R CD20+ FL received subcutaneous epcoritamab + R2 for 12 cycles (28 d/cycle). In the dose-escalation part of the trial, epcoritamab was administered at 24 or 48 mg; in the expansion part, the dose was 48 mg. Pts received their assigned epcoritamab dose as follows: every wk, cycles 1–3; every 2 wk, cycles 4–9; and every 4 wk, cycles ≥10 up to 2 y. Corticosteroid prophylaxis and step-up epcoritamab dosing were required during cycle 1 to mitigate CRS. PET-CT was used to assess response. All pts provided informed consent before enrollment. Results: As of the data cutoff date of December 1, 2021, 30 pts had received epcoritamab (24 mg, n=3; 48 mg, n=27) + R2. Median age was 68 y. Overall, 70% of pts had stage IV disease, 67% had FLIPI scores 3–5, 30% had primary refractory disease, and 40% had disease progression within 24 mo after starting first-line treatment (20% within 24 mo after starting immunochemotherapy). The median number of prior lines of therapy was 1 (range, 1–5). With a median follow-up of 5.1 mo (range, 0.8–12.3), 25 pts (83%) remained on study treatment; 5 pts had discontinued due to disease progression (n=2), AEs (n=2), or withdrawal of consent (n=1). Frequent treatment-emergent AEs (TEAEs; any grade [G]) included infections (57%), injection-site reactions (50%), constipation (37%), fatigue (37%), and neutropenia (37%). CRS was reported in 15 pts (50%; G1 30%, G2 13%, G3 7%). Most CRS events occurred in cycle 1, and all CRS events resolved with standard management (median time to resolution, 3 d; range, 1–8). Tocilizumab was used in 3 pts with CRS, and 1 pt discontinued study treatment due to CRS. ICANS (G2) was reported in 1 pt and resolved. There were no fatal TEAEs. Response profiles for individual pts are shown in Figure 1. Among the efficacy-evaluable pts, the ORR was 100% (27/27), with 93% (25/27) achieving a complete metabolic response (CMR) and 7% (2/27) achieving a partial metabolic response. As of the data cutoff date, the longest duration of response was 7.0+ mo and ongoing. Image:Summary/Conclusion: Subcutaneous epcoritamab + R2 demonstrated promising efficacy in pts with R/R FL, with a high CMR rate. The safety profile remained consistent with prior data. CRS events occurred mostly in cycle 1 and were generally low grade. Updated data with 30 additional pts will be presented at the meeting.