FDA approves epcoritamab-bysp for follicular lymphoma indications

FDA approval (Nov 18, 2025)

The FDA approved epcoritamab-bysp (Epkinly; Genmab US, Inc.) in combination with lenalidomide and rituximab (R2) for relapsed or refractory follicular lymphoma (FL).

The FDA also granted traditional approval to epcoritamab-bysp as monotherapy for relapsed or refractory FL after ≥2 lines of systemic therapy (this monotherapy indication received accelerated approval in 2024).

Supporting evidence: EPCORE FL-1

Combination approval was based on EPCORE FL-1 (Study M20-638; NCT05409066), a randomized, open-label trial enrolling 488 patients with relapsed or refractory FL. Patients were randomized 1:1 to epcoritamab-bysp + R2 vs R2 alone. Median prior systemic therapy lines: 1 (range 1–7); 24% had 2 prior lines and 17% had ≥3.

Efficacy (IRC-assessed Lugano 2014) favored the epcoritamab-bysp arm:

• PFS HR 0.21 (95% CI 0.13–0.33; p < 0.0001); median PFS NR (95% CI 21.9 mo–NR) vs 11.2 mo (95% CI 10.5–NR)
• ORR 89% (95% CI 84–93) vs 74% (95% CI 68–79)

Safety and dosing highlights

Prescribing information includes boxed warnings for CRS and ICANS; warnings/precautions for infections and cytopenias. Serious adverse reactions occurred in 51% (serious infections 28%); CRS 24% (serious 12%); ICANS 0.8%.

Recommended combination regimen: subcutaneous epcoritamab-bysp up to 12 28-day cycles with lenalidomide (Days 1–21 each cycle) and rituximab (5 cycles), using a Cycle 1 step-up schedule to 48 mg, then weekly (Cycles 2–3) and every 4 weeks (Cycles 4–12).