Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma:Phase 1/2 Trial Update

Background: For patients with relapsed or refractory (R/R) follicular lymphoma (FL), therapies such as rituximab + lenalidomide (R²) have demonstrated efficacy and acceptable safety. However, better treatments are needed to help more patients achieve deeper and more durable responses. Epcoritamab is a subcutaneously administered bispecific antibody that simultaneously binds to CD3 on T cells and CD20 on B cells to kill malignant B cells. R² and epcoritamab have nonoverlapping toxicity profiles and, therefore, may be safely combined. In addition, the immunomodulatory properties of lenalidomide may enhance the therapeutic potential of epcoritamab. Preliminary results from arm 2b of the phase 1/2 EPCORE NHL-2 trial (NCT04663347), which tested R² and epcoritamab in patients with R/R FL, showed an overall response rate of 93% and a complete metabolic response rate of 61% at the first assessment (6 wk; Falchi et al, ASCO 2022). Here we present updated data on a larger cohort and longer follow-up from arm 2b of EPCORE NHL-2.

Methods: Adults with R/R CD20⁺ FL were treated with subcutaneous epcoritamab 48 mg + standard R² for 12 cycles of 28 d each. Epcoritamab was dosed as follows: QW, cycles 1 and 2; Q4W, cycles ≥3 up to 2 y. Step-up epcoritamab dosing and corticosteroid prophylaxis were required during cycle 1 to mitigate CRS. PET-CT was used to assess responses per Lugano 2014 criteria.

Results: As of the data cutoff date of June 10, 2022, 62 patients had received epcoritamab (48 mg) + R². The median age was 65 y (range, 30-79), 58% of patients had stage IV disease, 52% had FLIPI 3-5, 31% had primary refractory disease, and 47% had experienced disease progression within 24 mo after starting first-line treatment. Half of patients (50%) had received 1 prior line of therapy (range, 1-9). Treatment was ongoing in 56 patients (90%), with a median follow-up of 4.0 mo. Six patients discontinued therapy due to disease progression (n=4) or other reasons (death due to COVID-19, n=1; reason unknown, n=1). The most common treatment-emergent AEs of any grade were CRS (37%; 27% grade 1, 10% grade 2, no grade 3-4), neutropenia (29%; 5% grade 1-2, 24% grade 3-4), fatigue (26%; 24% grade 1-2, 2% grade 3-4), and injection-site reactions (26%; all grade 1-2). Most CRS events (in 35% of all evaluable patients) occurred after the first full dose of epcoritamab. All CRS events resolved (median time to resolution, 2 d; range, 1-4), no patients discontinued treatment due to CRS, and 5 patients received tocilizumab. ICANS (grade 1) occurred in 1 patient 22 d from the start of treatment, and it resolved in 7 d. There were no clinical tumor lysis syndrome events. Among 41 efficacy-evaluable patients, the overall response rate was 95% (39/41), with 73% of patients (30/41) achieving a complete metabolic response (CMR) as their best overall response. Most CMRs (27/30) were achieved by the first assessment (6 wk), and nearly all (29/30) were ongoing at the time of data cutoff. Of the 9 patients with a partial metabolic response, 6 had an ongoing response at the time of data cutoff. The longest duration of response was 4.5+ mo. Median progression-free survival was not reached (Figure).

Conclusions: In patients with R/R FL, subcutaneous epcoritamab + R² demonstrated a manageable safety profile with only low-grade CRS events, mostly observed following the first full dose and all of which resolved. No new safety signals were detected. Data from this cohort are very encouraging with a high CMR rate observed in patients with R/R FL. These data are consistent with prior results from the EPCORE NHL-2 trial and supportive of ongoing investigation of epcoritamab + R² in patients with R/R FL. A phase 3 trial of epcoritamab + R² compared with R² alone in patients with R/R FL (EPCORE FL-1) will open in 2022.

Falchi:Genetech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Research Funding; Genmab: Consultancy, Research Funding. Abrisqueta:Sandoz: Honoraria; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy. Nijland:Genmab: Consultancy; Takeda: Research Funding; Roche: Research Funding. Leppä:Nordic Nanovector: Research Funding; Genmab: Research Funding; Beigene: Consultancy; Pfizer: Consultancy; Orion Pharma: Consultancy; Bayer: Research Funding; BMS: Consultancy, Research Funding; Gilead Sciences: Consultancy, Honoraria; Roche: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria. Hutchings:Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Incyte: Research Funding; Genmab: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; AbbVie: Consultancy; Janssen: Consultancy, Research Funding; Novartis: Research Funding; Genentech: Research Funding; Celgene, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, Takeda: Research Funding; AbbVie, Celgene, Genmab, Janssen, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees. Holte:Gilead: Honoraria, Other: Advisory board; Nordic Nanovector: Honoraria, Other: Safety committee; Takeda: Honoraria, Other: Advisory board; Incyte: Honoraria, Other: Advisory board; Genmab: Honoraria, Other: Safety committee; Novartis: Honoraria, Other: Advisory board. Merryman:Bristol Myers Squib: Consultancy, Research Funding; Abbvie: Consultancy; Intellia: Consultancy; Epizyme: Consultancy; Merck & Co., Kenilworth, NJ: Research Funding; Genentech/Roche: Research Funding; Pfizer: Research Funding; Adaptive Biotechnologies: Consultancy; Genmab: Consultancy, Research Funding. Lugtenburg:Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. de Vos:BeiGene: Other: Participation on a Data Safety Advisory Board. Cheah:Novartis: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Ascentage Pharma: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel expenses, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Arcaini:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene/Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees. Drott:Respiratorius AB: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Honoraria; Roche: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celegene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Jansssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Karyopharm: Speakers Bureau; Eli Lily: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Vitolo:Abbvie, Incyte, Janssen, Servier: Speakers Bureau; Gilead, Incyte, Genmab, Bayer, Constellation, Seattle-Genetics: Membership on an entity's Board of Directors or advisory committees. Rana:Genmab: Current Employment. Abbas:Genmab: Current Employment. Wang:Genmab: Current Employment. Dinh:AbbVie: Current Employment, Current equity holder in publicly-traded company. Belada:Genmab: Research Funding.