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

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, Minh Dinh¹⁵, David Soong¹⁶, Hidehisa Noguchi¹⁷, Jeppe Klint Buchbjerg¹⁸, Elena Favaro¹⁹, Noriko Fukuhara²⁰

Affiliations

¹ Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
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, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 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 and Oncology, 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 Oncology Clinical Development, AbbVie, North Chicago, Illinois, USA.
¹⁶ Translational Data Science, Genmab, Plainsboro, New Jersey, USA.
¹⁷ Biostatistics, Genmab, Tokyo, Japan.
¹⁸ Clinical Research Scientists, Genmab, Copenhagen, Denmark.
¹⁹ Medical Hematology, Genmab, Copenhagen, Denmark.
²⁰ Department of Hematology, Tohoku University, Sendai, Japan.

PMID: 37921363
PMCID: PMC10728012
DOI: 10.1111/cas.15996

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

Koji Izutsu et al. Cancer Sci. 2023 Dec.

. 2023 Dec;114(12):4643-4653.

doi: 10.1111/cas.15996. Epub 2023 Nov 3.

Authors

Affiliations

¹ Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
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, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 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 and Oncology, 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 Oncology Clinical Development, AbbVie, North Chicago, Illinois, USA.
¹⁶ Translational Data Science, Genmab, Plainsboro, New Jersey, USA.
¹⁷ Biostatistics, Genmab, Tokyo, Japan.
¹⁸ Clinical Research Scientists, Genmab, Copenhagen, Denmark.
¹⁹ Medical Hematology, Genmab, Copenhagen, Denmark.
²⁰ Department of Hematology, Tohoku University, Sendai, Japan.

PMID: 37921363
PMCID: PMC10728012
DOI: 10.1111/cas.15996

Abstract

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.

Keywords: B-cell lymphoma; CD20 antigen; CD3 antigen; bispecific antibody; diffuse large B-cell lymphoma.

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Conflict of interest statement

Koji Izutsu has received honoraria/fees from Janssen and Ono Pharmaceutical and research funding from AbbVie, Incyte Biosciences, Bristol Myers Squibb, Novartis, Janssen, Yakult, Daiichi Sankyo, Chugai, BeiGene, and Genmab. Hirokazu Nagai has received 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 has received honoraria/fees from Chugai and Roche and scholarship endowments/academic research funding from Takeda, Eisai, and Bristol Myers Squibb. Youko Suehiro has received research funding from Chugai, Genmab, Incyte, Amgen, Otsuka, AbbVie, Kyowa Kirin, and All Japan Pharma. Kazuhito Yamamoto has received honoraria/fees from AbbVie, Chugai, Eisai, HUYA, IQVIA, Janssen, Meiji Seika Pharma, Micron, Daiichi Sankyo, and Takeda and research funding from Genmab, IQVIA, and Yakult. Kenichi Ishizawa has received honoraria/fees from Bristol Myers Squibb, Chugai, Eisai, and Novartis and research funding from Pfizer, SymBio, AbbVie, Chugai, and Zenyaku. Takayuki Ikezoe has received 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 has received honoraria/fees from Chugai and Janssen and research funding from SymBio. Minh Dinh is an employee of AbbVie. David Soong, Hidehisa Noguchi, Jeppe Klint Buchbjerg, and Elena Favaro are employees of Genmab. Noriko Fukuhara has received honoraria/fees from Bristol Myers Squibb, Chugai, HUYA, and SymBio and research funding from AbbVie, Bayer, Celgene, Chordia, Chugai, Genmab, Incyte, Kyowa Kirin, Loxo Oncology, and Takeda. The other authors have no conflict of interest. The study was funded by Genmab A/S and AbbVie. Epcoritamab was provided by Genmab A/S and AbbVie. Genmab A/S and AbbVie collected and analyzed the data and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

Figures

**FIGURE 1**
Time on epcoritamab treatment among Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma who responded to treatment. Response based on independent review committee and Lugano criteria. Per protocol, patients continued to receive scans if they discontinued treatment for reasons other than progressive disease (PD). If patients had PD per Lugano criteria but indeterminate response per Lymphoma Response to Immunomodulatory Therapy Criteria, a follow‐up scan was completed to confirm disease progression. AE, adverse event; CR, complete response; PR, partial response; SD, stable disease.

**FIGURE 2**
Best percentage change from baseline in the sum of the products of perpendicular diameters of target lesions in Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma treated with epcoritamab. Evaluated per Lugano PET criteria. ASCT, autologous stem cell transplantation; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease. ^aOne patient did not have a confirmed sum of the products of perpendicular diameters and is not shown.

**FIGURE 3**
Kaplan–Meier curve for duration of response in Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma treated with epcoritamab.

**FIGURE 4**
Kaplan–Meier curve for progression‐free survival (PFS) in Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma treated with epcoritamab.

**FIGURE 5**
Kaplan–Meier curve for overall survival (OS) in Japanese adults with relapsed/refractory diffuse large B‐cell lymphoma treated with epcoritamab.

See this image and copyright information in PMC

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This study was funded by Genmab A/S and AbbVie.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials