FDA Granted Second Approval for Epkinly to Treat Patients With Relapsed or Refractory Follicular Lymphoma

On June 26, 2024, the FDA approved epcoritamab-bysp (Epkinly; Abbvie and Genmab) as the first and only T-cell engaging bispecific antibody administered subcutaneously for the treatment of adults with relapsed or refractory follicular lymphoma (FL) after ≥2 lines of prior therapy. This indication was approved under the FDA's accelerated approval program based on overall response rate (ORR) and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

"The FDA approval of Epkinly offers a new treatment option for relapsed or refractory follicular lymphoma, particularly following failure of other therapies," said Mariana Cota Stirner, MD, PhD, vice president, therapeutic area head for hematology, AbbVie. "Epkinly treatment has shown deep and durable responses for many patients. Subcutaneous dosing offers convenience, and Epkinly can be given to patients without mandatory hospitalization using a 3-step-up dosing regimen. We believe that Epkinly has the potential to be a core therapy in the treatment of multiple B-cell malignancies and furthers our company mission to advance research to raise standards of care for patients with cancer."

Epcoritamab is being codeveloped by AbbVie and Genmab as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the United States and Japan, and AbbVie will be responsible for further global commercialization.

FL is typically an indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes. Many people living with FL who have relapsed or are refractory to existing therapies have limited treatment options and reduced survival.¹ FL is the second most common form of NHL accounting for 20% to 30% of all cases.² About 15,000 people develop FL each year in the United States,³ and it is considered incurable with current standard of care therapies.⁴ Patients often relapse and, with each relapse the remission and time to next treatment is shorter.⁵ Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.⁶

"Patients with relapsed or refractory follicular lymphoma face significant treatment challenges, and there is currently no clear standard of care treatment available across practice settings," said Jeff Sharman, MD, Disease Chair, Hematology Research, Sarah Cannon Research Institute at Willamette Valley Cancer Institute in Eugene, Oregon. "The responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, as well as in patients with relapsed or refractory DLBCL from the trial, show the potential of Epkinly to serve as an important treatment option for these patients."

Lee Greenberger, PhD, Chief Scientific Officer at The Leukemia & Lymphoma Society, added, "People living with follicular lymphoma are in need of additional options when their cancer returns. Today's approval is welcome news for patients, as it provides another tool in the physician arsenal for this difficult-to-treat form of cancer."

FDA approval is based on results from the Phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of epcoritamab-bysp in 127 adult patients with relapsed or refractory FL who previously received a median of 3 lines of therapy; 70% of the cohort had double refractory disease.

EPCORE NHL-1 Efficacy and Safety Findings

• The study's primary end point, ORR, was 82%—the complete response rate was 60% and the partial response rate was 22%.
• At a median follow-up of 14.8 months among responders, more than half of patients who responded to treatment in the study remained responsive to treatment (ie, median duration of response was not reached).
• Safety was evaluated in 213 patients
  • The safety of epcoritamab-bysp at a target dose of 48 mg was evaluated in EPCORE NHL-1, a single-arm study of 127 patients who received a 2-part step-up dosage schedule.
  • The most common (≥20%) adverse reactions were injection site reactions, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache.
  • A separate dose optimization cohort evaluated 86 patients at the recommended 3-step dosage schedule for CRS mitigation. For the first full dose of this 3-step regimen, mandatory hospitalization was not required. No cases of grade 3 CRS were observed in patients with FL who received epcoritamab-bysp with the 3-part step-up dosage schedule.

The prescribing information has a boxed warning for serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome. Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. Please see the prescribing information for additional important safety information.

1. Salles G, Schuster S, Fischer L, et al. A retrospective cohort study of treatment outcomes of adult patients with relapsed or refractory follicular lymphoma (ReCORD-FL). HemaSphere. 2022;6(7):e745.
2. Lymphoma Research Foundation official website. Accessed February 2024. https://lymphoma.org/aboutlymphoma/nhl/fl/
3. Leukemia & Lymphoma Society. Accessed March 2024. https://www.lls.org/research/follicular-lymphoma-fl
4. Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832.
5. Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol. 2018;184(5):753-759.
6. Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008;26(32):5165-5169.