FDA grants accelerated approval to epcoritamab-bysp for relapsed or refractory follicular lymphoma
Regulatory approval: On June 26, 2024, the FDA granted accelerated approval to subcutaneous epcoritamab-bysp (Epkinly), a CD20-directed CD3 T-cell engager, for adults with relapsed or refractory follicular lymphoma after ≥2 prior systemic therapy lines. Approval was based on the single-arm EPCORE NHL-1 trial (NCT03625037), where ORR was 82% with 60% complete responses; median duration of response was not reached at 14.8 months’ median follow-up among responders. A confirmatory phase 3 trial is ongoing.
FDA accelerated approval (2024-06-26): epcoritamab-bysp in R/R follicular lymphoma
The US FDA granted accelerated approval on June 26, 2024 to epcoritamab-bysp (Epkinly; Genmab US, Inc.), a bispecific CD20-directed CD3 T-cell engager, for adult patients with relapsed or refractory follicular lymphoma after ≥2 lines of systemic therapy.
Key efficacy evidence (EPCORE NHL-1; NCT03625037)
- Design: Open-label, multi-cohort, multicenter, single-arm trial.
- Population: 127 patients with R/R FL after ≥2 systemic therapy lines (primary efficacy/safety population; 2 step-up regimen). An additional 86-patient dose-optimization cohort evaluated the recommended 3 step-up regimen for CRS mitigation.
- Endpoints: ORR and DOR by Independent Review Committee using Lugano 2014 criteria.
- Results (n=127): ORR 82% (95% CI, 74.1–88.2) with 60% complete responses; with estimated median follow-up of 14.8 months among responders, estimated median DOR not reached (95% CI, 13.7–NR); 12-month DOR estimate 68.4% (95% CI, 57.6%–77.0). Efficacy was reported as similar in the 86-patient 3-step cohort.
Safety and labeling highlights
- Boxed Warning: serious or fatal CRS and ICANS.
- Warnings/Precautions: serious infections and cytopenias.
- Reported rates: ICANS 6.0%; serious infections 40%. In the 86 patients receiving the recommended 3-step regimen, CRS occurred in 49%, all grade 1 (45%) or grade 2 (9%).
Post-approval requirement
As an accelerated approval, clinical benefit verification is pending; a phase 3 randomized trial (NCT05409066) is ongoing and reported to be ~95% enrolled, evaluating rituximab/lenalidomide alone or with epcoritamab-bysp in R/R FL.