Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial PMID: 36548927

Target-related Cytokines

2026-09-23

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial

J Clin Oncol. 2023 Apr 20;41(12):2238-2247. doi: 10.1200/JCO.22.01725.

Catherine Thieblemont ¹ , Tycel Phillips ² , Herve Ghesquieres ³ , Chan Y Cheah ⁴ ⁵ , Michael Roost Clausen ⁶ , David Cunningham ⁷ , Young Rok Do ⁸ , Tatyana Feldman ⁹ , Robin Gasiorowski ¹⁰ , Wojciech Jurczak ¹¹ , Tae Min Kim ¹² , David John Lewis ¹³ , Marjolein van der Poel ¹⁴ , Michelle Limei Poon ¹⁵ , Mariana Cota Stirner ¹⁶ , Nurgul Kilavuz ¹⁷ , Christopher Chiu ¹⁷ , Menghui Chen ¹⁷ , Mariana Sacchi ¹⁷ , Brian Elliott ¹⁷ , Tahamtan Ahmadi ¹⁷ , Martin Hutchings ¹⁸ , Pieternella J Lugtenburg ¹⁹

Affiliations

1. Assistance Publique & Hôpitaux de Paris (APHP), Hôpital Saint-Louis, Hémato-oncologie, Université de Paris, Paris, France.
2. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
3. Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
4. Sir Charles Gairdner Hospital, Perth, Australia.
5. Division of Internal Medicine, Medical School, University of Western Australia, Perth, Australia.
6. Vejle Hospital, Vejle, Denmark.
7. The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
8. Keimyung University Dongsan Medical Center, Daegu, Republic of Korea.
9. Hackensack Meridian Health Hackensack University Medical Center, Hackensack, NJ.
10. Concord Hospital, University of Sydney, Sydney, Australia.
11. MSC National Research Institute of Oncology, Kraków, Poland.
12. Seoul National University Hospital, Seoul, Republic of Korea.
13. University Hospitals Plymouth NHS Trust, Derriford Hospital, Plymouth, United Kingdom.
14. On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Maastricht, Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
15. National University Hospital, Singapore.
16. AbbVie, North Chicago, IL.
17. Genmab, Princeton, NJ.
18. Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
19. On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC, Erasmus MC Cancer Institute, University Medical Center, Department of Hematology, Rotterdam, the Netherlands.

Abstract

Purpose: Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20⁺ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell Non-Hodgkin Lymphoma subtypes.

Patients and methods: In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20⁺ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee.

Results: As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20-83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event.

Conclusion: Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.