Subcutaneous (SC) Epcoritamab (GEN3013; DuoBody-CD3xCD20) in patients with relapsed/refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL): dose-escalation data from a phase I/II Trial
Hutchings, M. Lugtenburg, P. Mous, R. Clausen, M. R. Chamuleau, M. Rule, S. Lopez, J. Oliveri, R. S. DeMarco, D.
Hutchings, M.
Lugtenburg, P.
Mous, R.
Clausen, M. R.
Chamuleau, M.
Rule, S.
Lopez, J.
Oliveri, R. S.
DeMarco, D.
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Abstract
Context: CD3×CD20 bispecifi c antibodies (bsAbs) have demonstrated promising results in R/R B-NHL. Epcoritamab is a novel subcutaneously-administered bsAb with a favorable safety profi le and encouraging preliminary anti-tumor activity in both aggressive and indolent B-NHL in a Phase I/II trial (NCT03625037). Objective: Determine recommended phase 2 dose, safety, and anti-tumor activity of epcoritamab. Participants: Adults with R/R CD20+ B-NHL. Intervention: SC 1 mL injection of fl at-dose epcoritamab (dosing escalation range 0.0128–48 mg preceded by a priming and intermediate dose) administered in 28-day cycles until disease progression or unacceptable toxicity. Results: As of 24 April 2020, 58 patients with a median (range) age 68 (21–84) years were enrolled. Most patients had DLBCL (67.2%) or FL (19.0%) and received a median (range) of 3 (1–6) and 5 (1–18) prior lines of treatment, respectively. No dose-limiting toxicities were observed (median follow-up [range]: 2.7 [ 0.2–16.4] months). MTD has not been reached. Majority of TEAEs were mild (Grade 1–2); the most common TEAEs (>35%) were pyrexia (69.0%), fatigue (41.4%), and injection site reaction (41.4%; all Grade 1). AEs of special interest included CRS (56.9%; no Grade 3 events occurred; all resolved) and neurotoxicity (6.9%; median [range] duration of events: 1 [<1– 3] day). There was no tumor lysis syndrome, neutropenic fever, or treatment-related death. Treatment is ongoing in 20 patients. Antitumor activity (14 May 2020) in evaluable patients with DLBCL (12mg) and FL (0.76mg) are: DLBCL (n=15): ORR 60.0% (CR: 20.0%; PR: 40.0%), SD: 6.7%, PD: 33.3%. FL (n=7): ORR 85.7% (PR: 85.7%), SD: 14.3%, no patients with PD. One patient with DLBCL de novo achieved a response post-data cutoff. Median (range) time to response was 1.6 (1–4) months. Conclusions: The safety, effi cacy, and pharmacokinetics data support epcoritamab 48 mg SC (1 mL, single dose) to be explored in the expansion phase. SC epcoritamab continues to demonstrate a favorable safety profi le consistent with previous reported data. Notably, there were no treatment-related deaths, no febrile neutropenia, tumor lysis syndrome, or Grade 3 CRS events. Epcoritamab has the potential for outpatient administration. Epcoritamab induces rapid, deep responses in heavily pretreated patients across different B-NHL subtypes.
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Date
2020
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Collections
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Type
Meetings and Proceedings
Citation
Hutchings M, Lugtenburg P, Mous R, Clausen MR, Chamuleau M, Linton KM, et al. Subcutaneous (SC) Epcoritamab (GEN3013; DuoBody-CD3xCD20) in patients with relapsed/refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL): dose-escalation data from a phase I/II Trial. Clinical Lymphoma Myeloma & Leukemia. 2020;20:S274-S.