Subcutaneous Epcoritamab Effective in Patients with Relapsed or Refractory Large B-Cell Lymphoma

Take-aways:

• Epcoritamab is a subcutaneous CD3/CD20 bispecific antibody that induces anti-tumor activity across B-cell NHL subtypes.
• The study showed that epcoritamab is effective in patients with relapsed or refractory large B-cell lymphoma.
• While efficacy was observed in both CAR-T–exposed and –naïve patients, a numerically higher percentage of the latter responded to single-agent epcoritamab.

---

Late-breaking preliminary results from the large B-cell lymphoma (LBCL) expansion cohort in the phase II EPCORE NHL-1 study of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) showed that the off-the-shelf therapy demonstrated clinically meaningful results in this difficult-to-treat population.

As of January 31, 2022, the study had expanded to 157 patients with diffuse LBCL (including double/triple-hit and transformed), high-grade B-cell lymphoma, primary mediastinal LBCL, or grade 3b follicular lymphoma. Patients were treated with epcoritamab, a novel, subcutaneous CD3/CD20 bispecific antibody that induces anti-tumor activity across B-cell NHL subtypes in dose escalation as a single agent and in combination with various standards of care.

In the study, adults with relapsed or refractory CD20+ LBCL received epcoritamab (priming and intermediate doses followed by full doses of 48 mg) 1 mL subcutaneous (SC) injections in cycles of 28 days until disease progression or unacceptable toxicity. Measures to mitigate cytokine release syndrome (CRS) included step-up dosing and corticosteroid prophylaxis. Overall, 61% of patients had primary refractory disease, and 83% were refractory to the last line of therapy.

At a median follow-up of 10.7 months, the overall response rate (ORR) by Independent Review Committee based on Lugano criteria and assessed by positron emission tomography/computed tomography was 63%, including 39% complete responses (CRs). The ORR and CR rates were 69% and 42% for chimeric antigen receptor (CAR) T-cell–naïve patients and 54% and 34% for patients who previously received CAR-T therapy. The ORR was similar across subgroups, regardless of age, prior line of therapy, and de novo or transformed disease status.

Most CRS events were low grade and occurred during the first injection cycle, and immune effector cell-associated neurotoxicity syndrome was limited, accounting for one patient death. A total of 12 patients (7.6%) experienced treatment-emergent adverse events that led to treatment discontinuation, the most common of which were CRS, pyrexia, fatigue, and neutropenia.

“Epcoritamab is a convenient, SC, off-the-shelf therapy that demonstrated clinically meaningful and compelling efficacy including deep and durable responses in a challenging-to-treat, highly refractory LBCL population,” the authors concluded.

Reference

Thieblemont C, Phillips T, Ghesquieres H, et al. Primary results of subcutaneous epcoritamab dose expansion in patients with relapsed or refractory large B-cell lymphoma: a phase 2 study. Abstract #LB2364. Presented at the 2022 European Hematology Association Congress, June 9-12, 2022.