FDA approves Epkinly (epcoritamab) injection treatment for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma

FDA has approved Epkinly (epcoritamab-bysp) injection (Abbivie) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma after two or more lines of systemic therapy.

target/MOA: IgG1-bispecific antibody CD3xCD20

FDA granted accelerated approval to Epkinly. This marked the first time a T-cell engaging bispecific antibody was approved. This application was granted priority review and used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. 

Of note:

·         Epkinly is administered subcutaneously (under the skin) in 28-day cycles until disease progression or unacceptable toxicity. The recommended dose is detailed in the prescribing information.

·         Phase 3 randomized controlled trial is ongoing to confirm clinical benefit

Strong uptake is expected due to epcoritamab subcutaneous formulation, strong efficacy, as well as the targeting of both the CART in-eligible and the post-CART population, currently a high unmet need in the DLBCL space. Bispecifics may also present opportunities for novel combinations with the CD47 MoA in certain patient populations.

Studies

PCORE NHL-1 (NCT03625037) is an open-label, multi-cohort, multicenter, Phase 1/2 single-arm trial.

The efficacy population consisted of 148 patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after two or more lines of systemic therapy, including at least one anti-CD20 monoclonal antibody-containing therapy. Note, 29% of patients were refractory to CAR-T cell therapy.

The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) per Lugano 2014 criteria.

Epkinly demonstrated an overall response rate (ORR) of 61% (95% CI: 53, 69), a complete response rate of 38%, and median duration of response (DOR) of 15.6 months (95% CI: 9.7, not reached).

The most common adverse reactions (≥20%) were cytokine release syndrome (CRS), fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. 

Among the 157 patients with relapsed or refractory large B-cell lymphoma who received Epkinly, CRS occurred in 51% of patients, immune effector cell-associated neurotoxicity syndrome (ICANS) in 6%, and serious infections in 15%.

Full FDA page