KEY TAKEAWAYS
- The Phase 1 &2 trials aimed to investigate the efficacy and safety of epcoritamab monotherapy in patients with multiple R/R FL.
- The primary endpoint was to determine the ORR independently.
- Researchers noticed that epcoritamab demonstrated significant efficacy and manageable safety in R/R FL.
A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory (R/R) follicular lymphoma (FL).
Kim M. Linton and the team aimed to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the 3-line and later setting of FL.
They performed an inclusive analysis in the EPCORE NHL-1 trial, a multicohort, single-arm, phase 1-2 study conducted at 88 sites across 15 countries. The primary analysis focused on patients with R/R FL in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimization cohort.
Eligible patients were aged 18 years or older, had R/R CD20+ FL (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least 2 previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide).
The patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0.16-mg priming dose on day 1 and a 0.80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg.
In the cycle 1 optimization cohort, a 2 intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce the risk and severity of cytokine release syndrome.
The primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimization cohort. Analyses were conducted in all enrolled patients who had received at least 1 dose of epcoritamab.
About 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort between June 19, 2020, and April 21, 2023, with a median follow-up of 17.4 months (IQR 9.1-20.9). The overall response rate was 82.0% (105 of 128 patients; 95% CI 74.3-88.3), with a complete response rate of 62.5% (80 of 128; 95% CI 53.5-70.9). The most common grade 3-4 treatment-emergent adverse event was neutropenia, occurring in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients, with grade 3 cytokine release syndrome reported in 2 (2%) patients.
Immune effector cell-associated neurotoxicity syndrome was reported in 8 (6%) of 128 patients (5 [4%] grade 1; 3 [2%] grade 2). Additionally, between October 25, 2022, and January 8, 2024, 86 patients (median age 64 years [IQR 55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimization cohort.
The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported cases of immune effector cell-associated neurotoxicity syndrome.
The study concluded that epcoritamab monotherapy demonstrated clinically meaningful activity in patients with multiple R/R FL and had a manageable safety profile.
The trial is sponsored by the Genmab.
Source: https://pubmed.ncbi.nlm.nih.gov/38889737/
Clinical Trial: https://clinicaltrials.gov/study/NCT03625037
Linton KM, Vitolo U, Jurczak W, et al. (2024). “Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study.” Lancet Haematol. 2024 Aug;11(8):e593-e605. doi: 10.1016/S2352-3026(24)00166-2. Epub 2024 Jun 15. PMID: 38889737.
