P1135 SUBCUTANEOUS EPCORITAMAB IN COMBINATION WITH RITXUIMAB + LENALIDOMIDE IN RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA: PHASE 1/2 TRIAL UPDATE: David Belada1 , Sirpa Leppä2, Björn E. Wahlin3, Marcel Nijland4, Jacob Haaber Christensen5, Sven de Vos6, Harald Holte7, Kim M. Linton8, Aqeel Abbas 9, Liwei Wang9, Minh Dinh10, Brian Elliott 9, Lorenzo Falchi 11

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.
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.