Rapid Readout: Phase 1/2 Trial of Subcutaneous Epcoritamab With R-Squared in Patients with Relapsed or Refractory Follicular Lymphoma

Tycel Phillips, MD, discusses data from the following study:

• Subcutaneous Epcoritamab in Combination with R2 (Rituximab and Lenalidomide) in Patients with Relapsed or Refractory Follicular Lymphoma: Preliminary Results from a Phase 1/2 Trial. (ASH 2021, Dec 11-14. Poster 3535)
• The objective of EPCORE NHL-2 arm 2 is to report results of epcoritamab in combination with R2 in patients with relapsed/refractory follicular lymphoma (FL).
• R2 has immunomodulatory properties that may potentiate the activity of epcoritamab, suggesting that combining R2 with epcoritamab may be beneficial.
• 29 adults with relapsed/refractory FL were enrolled to receive subcutaneous epcoritamab + standard R2 for 12 cycles of 28 days, followed by epcoritamab monotherapy, for a total of 2 years.
• Safety and efficacy outcomes were assessed in the population:
  • Best overall response (OR) rate was assessed at 100%, with complete metabolic response (CMR) at 81% and partial metabolic response at 19%.
  • As of November 3, 2021, the updated data-cutoff date, OR rate was 100% and CMR was 92%.
  • The median number of cycles initiated was 7 for 24 mg: 3 for 48 mg and 3 overall.
  • No dose-limiting toxicities (DLTs), immune effector cell-associated neurotoxicity syndrome (ICANS), clinical tumor lysis syndrome (TLS) events, or fatal treatment-emergent adverse events (TEAEs) were reported.
  • 6 TEAEs, 3 of which were cytokine-release syndrome (CRS), led to epcoritamab dose delays.
  • All CRS events resolved with standard management, and patients who experienced CRS mostly experienced it after cycle 1, day 15.
• Conclusions:
  • Preliminary data for subcutaneous epcoritamab in combination with R2 demonstrated a manageable safety profile with no DLTs, ICANS, or TLS events.
  • Response was seen in 100% of patients, with nearly all achieving early CMR and no relapses observed.
  • There were no cases of progressive disease.
  • These data support further studies of epcoritamab + R2 in relapsed/refractory FL; expansion cohort 2b will enroll up to approximately 80 additional patients.