Clinical Trial

. 2025 Aug;30(8):1631-1640.

doi: 10.1007/s10147-025-02788-0. Epub 2025 May 28.

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial

Koji Izutsu¹, Takahiro Kumode², Junichiro Yuda³, Hirokazu Nagai⁴, Yuko Mishima⁵, Youko Suehiro⁶, Kazuhito Yamamoto⁷, Tomoaki Fujisaki⁸, Kenji Ishitsuka⁹, Kenichi Ishizawa¹⁰, Takayuki Ikezoe¹¹, Momoko Nishikori¹², Daigo Akahane¹³, Jiro Fujita¹⁴, Pegah Jafarinasabian¹⁵, David Soong¹⁶, Barbara D'Angelo Månsson¹⁷, Ami Takahashi¹⁸, Elena Favaro¹⁷, Noriko Fukuhara¹⁹

Affiliations

¹ Department of Hematology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan. kizutsu@ncc.go.jp.
² Department of Hematology and Rheumatology, Kindai University, Osaka, Japan.
³ Departments of Hematology and Experimental Therapeutics, Office for the Promotion of Hematological Treatment Development, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁵ Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁶ Department of Hematology and Cell Therapy, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁷ Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
⁸ Department of Hematology, Japan Red Cross Society, Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁹ Department of Hematology and Rheumatology, Kagoshima University, Kagoshima, Japan.
¹⁰ Third Department of Internal Medicine, Yamagata University, Yamagata, Japan.
¹¹ Department of Hematology, Fukushima Medical University Hospital, Fukushima, Japan.
¹² Department of Hematology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹³ Department of Hematology, Tokyo Medical University, Tokyo, Japan.
¹⁴ Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹⁵ AbbVie, North Chicago, IL, USA.
¹⁶ Genmab, Plainsboro, NJ, USA.
¹⁷ Genmab, Copenhagen, Denmark.
¹⁸ Genmab, Tokyo, Japan.
¹⁹ Department of Hematology, Tohoku University, Sendai, Japan.

PMID: 40434509
PMCID: PMC12296760
DOI: 10.1007/s10147-025-02788-0

Clinical Trial

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial

Koji Izutsu et al. Int J Clin Oncol. 2025 Aug.

. 2025 Aug;30(8):1631-1640.

doi: 10.1007/s10147-025-02788-0. Epub 2025 May 28.

Authors

Affiliations

¹ Department of Hematology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan. kizutsu@ncc.go.jp.
² Department of Hematology and Rheumatology, Kindai University, Osaka, Japan.
³ Departments of Hematology and Experimental Therapeutics, Office for the Promotion of Hematological Treatment Development, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
⁵ Department of Hematology Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
⁶ Department of Hematology and Cell Therapy, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁷ Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
⁸ Department of Hematology, Japan Red Cross Society, Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁹ Department of Hematology and Rheumatology, Kagoshima University, Kagoshima, Japan.
¹⁰ Third Department of Internal Medicine, Yamagata University, Yamagata, Japan.
¹¹ Department of Hematology, Fukushima Medical University Hospital, Fukushima, Japan.
¹² Department of Hematology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
¹³ Department of Hematology, Tokyo Medical University, Tokyo, Japan.
¹⁴ Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹⁵ AbbVie, North Chicago, IL, USA.
¹⁶ Genmab, Plainsboro, NJ, USA.
¹⁷ Genmab, Copenhagen, Denmark.
¹⁸ Genmab, Tokyo, Japan.
¹⁹ Department of Hematology, Tohoku University, Sendai, Japan.

PMID: 40434509
PMCID: PMC12296760
DOI: 10.1007/s10147-025-02788-0

Abstract

Background: Primary results from the EPCORE NHL-3 trial (NCT04542824) showed deep, durable responses in Japanese patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with single-agent epcoritamab, a subcutaneous CD3xCD20 bispecific antibody. Here, we report 3-year follow-up of safety and efficacy.

Methods: Japanese patients with R/R CD20⁺ DLBCL and ≥ 2 prior systemic therapies received epcoritamab (0.16/0.8-mg step-up doses, then 48-mg full doses) according to the approved label. The primary endpoint was overall response rate per independent review committee.

Results: As of July 12, 2024, 36 patients received epcoritamab (median follow-up, 36.7 months). Overall/complete response rates were 56%/47%. Median duration of response was 15.2 months. Median duration of complete response was not reached; an estimated 53% of complete responders remained in complete response at 3 years. Median progression-free/overall survival (PFS/OS) were 4.1/14.9 months overall; neither was reached among complete responders. Three-year PFS/OS estimates were 25%/39% overall and 53%/71% in complete responders. Among 30 evaluable patients, 17 (57%) became minimal residual disease (MRD) negative, which was associated with longer PFS (cycle 3 day 1 landmark analysis). The most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (83%), injection-site reaction (69%), and neutropenia (39%), consistent with previous reports. No fatal TEAEs occurred.

Conclusions: With > 3 years of follow-up, epcoritamab treatment has consistently shown durable responses and high rates of MRD negativity in Japanese patients with R/R DLBCL. Safety was similar to previous reports. These long-term remissions reaffirm encouraging outcomes with epcoritamab for this challenging-to-treat population.

Keywords: B-cell lymphoma; Bispecific antibodies; Clinical trial; Non-Hodgkin lymphoma.

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Conflict of interest statement

Declarations. Conflict of interest: Koji Izutsu reports honoraria/fees from Janssen and Ono Pharmaceutical and research funding from AbbVie, Incyte, Bristol Myers Squibb, Novartis, Janssen, Yakult, Daiichi Sankyo, Chugai, BeiGene, and Genmab. Takahiro Kumode reports honoraria/fees from Janssen, AstraZeneca, AbbVie, Genmab, BeiGene, and Ono Pharmaceutical. Junichiro Yuda has nothing to disclose. Hirokazu Nagai reports honoraria/fees from Chugai, Janssen, Meiji Seika, and Ono Pharmaceutical and scholarship endowments/academic research funding from Chugai, AstraZeneca, Janssen, Genmab, AbbVie, Daiichi Sankyo, BeiGene, Eli Lilly, and Kyowa Kirin. Yuko Mishima reports honoraria/fees from Chugai and Roche and scholarship endowments/academic research funding from Takeda, Eisai, and Bristol Myers Squibb. Youko Suehiro reports research funding from Chugai, Genmab, Incyte, Amgen, Otsuka, AbbVie, Kyowa Kirin, and All Japan Pharma. Kazuhito Yamamoto reports honoraria/fees from AbbVie, Chugai, Eisai, HUYA, IQVIA, Janssen, Meiji Seika, Micron, Daiichi Sankyo, and Takeda and research funding from Genmab, IQVIA, and Yakult. Tomoaki Fujisaki has nothing to disclose. Kenji Ishitsuka has nothing to disclose. Kenichi Ishizawa reports honoraria/fees from Bristol Myers Squibb, Chugai, Eisai, and Novartis and research funding from Pfizer, SymBio, AbbVie, Chugai, and Zenyaku. Takayuki Ikezoe reports honoraria/fees from Chugai, Asahi Kasei, and Nippon Shinyaku; research funding from Asahi Kasei; and scholarship endowments/academic research funding from Asahi Kasei, Novartis, Alexion, Janssen, Dainippon Sumitomo, Nippon Shinyaku, Takeda, AbbVie, Incyte, Otsuka, and GSK. Momoko Nishikori reports honoraria/fees from Chugai and Janssen and research funding from SymBio. Daigo Akahane has nothing to disclose. Jiro Fujita has nothing to disclose. Pegah Jafarinasabian reports current employment at AbbVie. David Soong reports current employment and is a stockholder at Genmab. Barbara D’Angelo Månsson reports current employment and is a stockholder at Genmab. Ami Takahashi reports current employment and is a stockholder at Genmab. Elena Favaro reports current employment and is a stockholder at Genmab. Noriko Fukuhara reports honoraria/fees from Bristol Myers Squibb, Chugai, HUYA, and SymBio and research funding from AbbVie, Bayer, Bristol Myers Squibb, Chordia, Chugai, Genmab, Incyte, Kyowa Kirin, Loxo Oncology, and Takeda.

Figures

**Fig. 1**
Kaplan–Meier curves for DOR (a) and DOCR (b) per independent review committee assessment among Japanese adults with relapsed or refractory diffuse large B-cell lymphoma. CR complete response, *DOCR* duration of complete response, *DOR* duration of response

**Fig. 2**
Kaplan–Meier curves for PFS by response (a), OS by response (b), PFS in complete responders with MRD negativity (c), and OS in complete responders with MRD negativity (d) among Japanese adults with relapsed or refractory diffuse large B-cell lymphoma. PFS and response are per independent review committee assessment. MRD-negativity status was assessed in a cycle 3 day 1 landmark analysis. The landmark analysis included MRD-evaluable patients who, by cycle 3 day 1, had neither a PFS event nor death. Patients were stratified by MRD status and followed from cycle 3 day 1 until PFS event or death. *MRD* minimal residual disease, OS overall survival, *PFS* progression-free survival, PR partial response

See this image and copyright information in PMC

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Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial

Affiliations

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Research Materials