Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity
Clausen, M. R. Lugtenburg, P. Hutchings, M. Johnson, P. W. M. Lewis, D. J. Chamuleau, M. Balari, A. S. Cunningham, D. Elliott, B.
Clausen, M. R.
Lugtenburg, P.
Hutchings, M.
Johnson, P. W. M.
Lewis, D. J.
Chamuleau, M.
Balari, A. S.
Cunningham, D.
Elliott, B.
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Abstract
Background: Epcoritamab is a CD20xCD3 bispecific antibody that induces T-cell mediated killing of CD20–positive malignant B-cells. We present updated data, including progression-free survival (PFS) from the dose escalation part of the first-in-human phase 1/2 study of epcoritamab in pts with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT03625037). Methods: Adults with R/R CD20+ B-NHL received flat-dose 1 mL SC epcoritamab (step-up dosing approach) in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Step-up dosing and standard prophylaxis were used to mitigate severity of cytokine release syndrome (CRS). Results: At data cut off (1/31/2021), 68 pts with B-NHL were enrolled across histologies including diffuse large B-cell lymphoma (DLBCL; n = 46 [67.6%]; de novo and transformed), follicular lymphoma (FL; 12 [17.6%]), mantle cell lymphoma (MCL; 4 [5.9%]), and others (6 [8.8%]). Majority were heavily pretreated (median [range] prior lines: DLBCL, 3 [1–6]; FL, 4.5 [1–18]); including prior CAR-T (n = 6) and prior ASCT (n = 10). At median follow-up of 14.1 mo (DLBCL, 10.2 mo; FL, 15.2 mo), treatment was ongoing in 15 (22%) pts. Most common treatment-emergent adverse events (AEs) were pyrexia (69%), CRS (59%), and injection site reaction (47%). CRS events were all grade 1 or 2 and most occurred in cycle 1; neurotoxicity was limited (6%; grade 1: 3%; grade 3: 3%; all transient). One case of tumor lysis syndrome was observed (1.5%; grade 3); there were no cases of febrile neutropenia or treatment-related death. Overall response is shown for DLBCL ≥12 mg and ≥48 mg and FL ≥12 mg, corresponding to the minimal efficacy threshold (Table). Responses deepened over time (PR converted to CR: DLBCL, 6 pts; FL, 3 pts). Median time to response was 1.4 mo (DLBCL) and 1.9 mo (FL). Among DLBCL pts achieving CR with ≥6 mg (n = 11), none relapsed while on treatment. The median PFS for pts with DLBCL ≥12 mg (n = 22) was 9.1 mo (95% CI: 1.6, NE; median follow-up 9.3 mo) and for pts with DLBCL ≥48 mg (n = 11) median PFS was not reached (median follow-up 8.8 mo). Updated analyses will be presented. Conclusions: With longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. Notably no severe (grade ≥3) CRS events, no febrile neutropenia, and limited neurotoxicity was observed.
Affiliation
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Clausen MR, Lugtenburg P, Hutchings M, Johnson PWM, Linton KM, Lewis DJ, et al. Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity. Vol. 39, Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 7518–7518.