Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma

• Published in: Cancer science 2023-12, Vol.114 (12), p.4643-4653
• Main Authors: Izutsu, Koji, Kumode, Takahiro, Yuda, Junichiro, Nagai, Hirokazu, Mishima, Yuko, Suehiro, Youko, Yamamoto, Kazuhito, Fujisaki, Tomoaki, Ishitsuka, Kenji, Ishizawa, Kenichi, Ikezoe, Takayuki, Nishikori, Momoko, Akahane, Daigo, Fujita, Jiro, Dinh, Minh, Soong, David, Noguchi, Hidehisa, Buchbjerg, Jeppe Klint, Favaro, Elena, Fukuhara, Noriko
• Format: Article
• Language: English
• Subjects: Adult; Antigens; Antineoplastic Agents - therapeutic use; B-cell lymphoma; Bispecific antibodies; bispecific antibody; CD20 antigen; CD3 antigen; Cell number; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cytokine Release Syndrome - drug therapy; Cytokines; diffuse large B‐cell lymphoma; Drug dosages; Humans; Hypokalemia; Hypothesis testing; Japan; Lymphocytes; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Non-Hodgkin - drug therapy; Medical prognosis; Multicenter Studies as Topic; Neutropenia; Non-Hodgkin's lymphoma; Original; Patients; Prophylaxis; Response rates; Toxicity
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15996

Epcoritamab is a subcutaneously administered CD3xCD20 bispecific Ab that showed deep, durable responses with a manageable safety profile in patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) in the global multicenter pivotal phase II trial EPCORE NHL‐1. Here, we present results from the similar EPCORE NHL‐3 phase I/II trial evaluating epcoritamab monotherapy in Japanese patients with R/R CD20+ B‐cell non‐Hodgkin's lymphoma previously treated with two or more lines of therapy. Epcoritamab was dosed subcutaneously in 28‐day cycles; once weekly during cycles 1–3, every 2 weeks during cycles 4–9, and every 4 weeks from cycle 10 until disease progression or unacceptable toxicity. Step‐up dosing and cytokine release syndrome (CRS) prophylaxis were used during treatment cycle 1. As of January 31, 2022, 36 patients received treatment with 48 mg epcoritamab monotherapy. At a median follow‐up of 8.4 months, overall response and complete response rates by independent review committee were 55.6% and 44.4%, respectively. The median duration of response, duration of complete response, and overall survival were not reached at the time of data cut‐off. The most common treatment‐emergent adverse events of any grade were CRS (83.3%), injection‐site reactions (69.4%), infections (44.4%), neutropenia (38.9%), hypokalemia (27.8%), and decreased lymphocyte count (25.0%). Cytokine release syndrome occurrence was predictable; events were primarily low grade (grade 1–2), all resolved, and none led to treatment discontinuation. These encouraging results are consistent with previous findings and support the ongoing clinical evaluation of epcoritamab for the treatment of R/R DLBCL, including in earlier treatment lines. The EPCORE NHL‐3 phase I/II trial is evaluating the efficacy and safety of epcoritamab subcutaneous monotherapy in Japanese patients with relapsed or refractory (R/R) CD20+ B‐cell non‐Hodgkin's lymphoma previously treated with two or more lines of therapy. At a median follow‐up of 8.4 months, overall response and complete response rates by independent review committee in the diffuse large B‐cell lymphoma (DLBCL) expansion cohort (treated with epcoritamab 48 mg s.c.) were 55.6% and 44.4%, respectively, and the median duration of response, duration of complete response, and overall survival were not reached at the time of data cutoff; the safety profile was manageable. Results support the ongoing clinical evaluation of epcoritamab in Japanes