Fixed-Duration Epcoritamab + R2 Drives Deep and Durable Responses in Patients with Relapsed or Refractory Follicular Lymphoma: 2-Year Follow-up from Arm 2 of the Epcore NHL-2 Trial
Year: 2024
Type: conference-abstract
Abstract: Introduction: Epcoritamab, a CD3xCD20 bispecific antibody, has been approved as a single agent for the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma and follicular lymphoma (FL) after ≥2 lines of systemic therapy based on results from the phase 1/2 EPCORE® NHL-1 trial (NCT03625037). For patients (pts) with R/R FL, rituximab + lenalidomide (R2) is an approved and widely accepted regimen based on results from the AUGMENT trial (overall response rate [ORR], 78%; complete response [CR] rate, 34%; estimated 2-y progression-free survival [PFS], 58%). There exists a clear need for improvement of outcomes, especially for pts with high-risk features, including disease progression within 24 mo of first-line chemoimmunotherapy (POD24) or primary/double-refractory disease, for whom there is no established standard of care. Previously, in arm 2 of the EPCORE NHL-2 trial (phase 1b/2; NCT04663347), fixed-duration epcoritamab + R2 showed encouraging antitumor activity and a manageable safety profile in a large population of pts with R/R FL, including high-risk pts (Merryman et al, ASCO 2023). Here, we present long-term follow-up beyond 2 y and minimal residual disease (MRD) analysis for the first time. Methods: Adults with R/R CD20+ FL received subcutaneous epcoritamab + R2 for up to 12 cycles (Cs; 28 d each). Epcoritamab was administered with a 2-step (0.16 and 0.8 mg) step-up dosing (SUD) regimen in C1 and 48-mg full doses either QW in C1-3, Q2W in C4-9, and Q4W in C≥10 (arm 2a) or QW in C1-2 and Q4W in C≥3 (arm 2b) for up to 2 y. MRD analysis was performed on peripheral blood mononuclear cell samples collected at prespecified time points (clonoSEQ® assay, Adaptive Biotechnologies) and quantified as tumor clones detected per 1 x 106 nucleated cells. The primary endpoint was ORR per Lugano criteria. Results: As of May 15, 2024, 111 pts with R/R FL had received epcoritamab 48 mg + R2. Median age was 65 y, 61% had stage IV disease, and 57% had only 1 line of prior treatment. Most pts had received alkylating agents (93%) and anthracyclines (64%); 3% had received prior CAR T. At a median follow-up of 25.3 mo (range, 2.4+ to 34.1), 17 pts (15%) were still on treatment, 41 (37%) completed treatment per protocol, and 53 (48%) discontinued treatment (progressive disease, n=18; AEs, n=22; pt withdrawal, n=7; death, n=1; COVID-19 control measure, n=1; and other reason, n=4 [investigator decision]). The ORR was 96%, and CR rate was 87%. CR rates were similarly high regardless of high-risk features: primary refractory (n=39)/non-primary refractory (n=72), 90%/86%; double refractory (n=39)/non-double refractory (n=72), 82%/90%; POD24 (n=42)/non-POD24 (n=69), 79%/93%. Estimated 24-mo PFS and overall survival rates were 70% and 90%, respectively. At 24 mo, an estimated 69% of responders remained in response (duration of response; DOR), and an estimated 75% of complete responders remained in CR (duration of CR; DOCR). MRD status was assessed in 73 evaluable pts; of these, 64 (88%) became MRD negative. With the majority of pts being enrolled and treated during the global COVID-19 pandemic, COVID-19 was reported in 57% of pts and led to epcoritamab discontinuation in 11% of pts; COVID-19 events included 5 grade (G) 5 treatment-emergent AEs (TEAEs; COVID-19, n=3; COVID-19 pneumonia, n=2). The other most common TEAEs were neutropenia (62%) and CRS (51%). CRS events with this 2-step SUD regimen were mostly low grade (38% G1, 12% G2, 2% G≥3) and primarily occurred following the first full dose on C1D15; all resolved, and none led to epcoritamab discontinuation. ICANS occurred in 1 pt (G1) and resolved. Conclusions: With more than 2 y of follow-up, fixed-duration epcoritamab + R2 continued to show deep and durable responses (CR rate, 87%; estimated 24-mo DOCR, 75%) in pts with R/R FL, irrespective of high-risk features. Considering limitations of cross-trial comparisons, these results (estimated 2-y PFS, 70%) compare favorably with those reported for R2 alone in the AUGMENT trial (estimated 2-y PFS, 58%). The depth of responses was underscored by MRD negativity in 88% of evaluable pts. There were no new safety findings, and the safety profile remained consistent with previous reports. Epcoritamab + R2 is being studied further in the ongoing, randomized, phase 3 EPCORE FL-1 trial (NCT05409066).
Source: Blood
Authors: Lorenzo Falchi, Anna Sureda Balari, Sirpa Leppä, Joost S.P. Vermaat, Marcel Nijland, Jacob Haaber Christensen, Sven de Vos, Harald Holte, Reid W. Merryman, Pieternella Lugtenburg, Pau Abrisqueta Costa, Kim Linton, Gauri Sunkersett, Christopher Morehouse, Andrew J. Steele, Jennifer Marek, Liwei Wang, Daniela Hoehn, Martin Hutchings, David Belada
Institutions: Memorial Sloan Kettering Cancer Center, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universitat de Barcelona, University of Helsinki, Helsinki University Hospital, Leiden University Medical Center, University Medical Center Groningen, University of Groningen, Odense University Hospital, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, Los Angeles Medical Center, Oslo University Hospital, Dana-Farber Cancer Institute, Erasmus MC Cancer Institute, Vall d'Hebron Hospital Universitari, University of Manchester, The Christie NHS Foundation Trust, Cancer Research UK Manchester Centre, AbbVie (United States), Genmab (United States), University of Copenhagen, Rigshospitalet, University Hospital Hradec Králové
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405043036