Subcutaneous Epcoritamab Combined With Rituximab + Lenalidomide for the Treatment of Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update

Introduction:
Relapsed or refractory (R/R) follicular lymphoma (FL) has a poor prognosis and is associated with less-durable responses following each additional line of treatment. Although combination rituximab and lenalidomide (R ) has an acceptable safety profile and is effective in R/R FL, FL remains incurable; better options are needed to improve outcomes. Epcoritamab is a subcutaneously administered CD3xCD20 bispecific antibody that simultaneously binds to CD3 on T cells and CD20 on malignant B cells. Because epcoritamab and R have distinct mechanisms of action, combining these therapies may increase antitumor response. We present updated data from EPCORE NHL-2 arm 2a, which is assessing epcoritamab in combination with R in patients with R/R FL (phase 1/2 trial; NCT04663347).
Methods:
Adults with R/R CD20 FL received subcutaneous epcoritamab combined with R for 12 cycles of 28 d each; in the dose-escalation phase, epcoritamab was administered at 24 or 48 mg; in the expansion phase, epcoritamab was administered at 48 mg. Corticosteroids and step-up dosing of epcoritamab were required during cycle 1 to mitigate CRS. The epcoritamab regimen was: QW, cycles 1–3; Q2W, cycles 4–9; and Q4W, cycles ≥10 up to 2 y. PET-CT was used to evaluate response per Lugano 2014 criteria.
Results:
As of March 25, 2022, 30 patients (median age, 68 y) had received subcutaneous epcoritamab + R (24 mg, n=3; 48 mg, n=27), 20 patients (67%) had FLIPI scores 3–5, and 21 patients (70%) had stage IV disease. Nine (30%) patients had primary refractory disease, 12 (40%) had disease progression within 24 mo of initial therapy, and the median number of prior lines of therapy was 1 (range, 1–5). With a median follow-up of 8.6 mo (range, 3.3–14.6), 23 (77%) patients remained on treatment. The most common treatment-emergent AEs (TEAEs) of any grade included injection-site reactions (53%), CRS (50%), constipation (47%), neutropenia (47%), fatigue (40%), and cough (37%). CRS was mostly low grade (30% grade 1, 13% grade 2, 7% grade 3), most events were associated with the first full dose, and all cases resolved. Tocilizumab was used in 3 patients, and 1 patient discontinued treatment due to CRS. One (3%) patient had grade 2 ICANS, which resolved in 4 d and did not lead to discontinuation of epcoritamab. No fatal TEAEs were reported. Among efficacy-evaluable patients, the overall response rate was 100% (28/28), with 96% (27/28) achieving a complete metabolic response (CMR). Responses were typically achieved early in treatment and deepened over time, with 93% of 27 evaluable patients achieving a response at 6 wk, and 70% achieving a CMR at 6 wk.
Discussion:
Subcutaneous epcoritamab + R showed encouraging responses in patients with R/R FL. This treatment combination showed a manageable safety profile, with mainly low-grade CRS and all cases having resolved. These updated results support further exploration of epcoritamab + R in patients with R/R FL. Arm 2b, which uses a different dosing schedule (QW, cycle 1–2; Q4W, cycles ≥3 up to 2 y), will also be presented.