P2059 MINIMAL RESIDUAL DISEASE (MRD), PHARMACOKINETIC (PK), AND PHARMACODYNAMIC (PD) ASSESSMENT OF EPCORITAMAB 2- VS 3-STEP STEP-UP DOSING IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (R/R FL)

Kim Linton

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Abstract

Background:
In the pivotal EPCORE™ NHL1 trial (phase 1/2; NCT03625037), epcoritamab treatment (tx) with a 2-step stepup dose (SUD) regimen led to high overall and complete response rates of 82% and 63%, respectively, in
patients with R/R FL. Safety was manageable, with CRS events being primarily low grade. However, further
mitigation of CRS may enhance the accessibility of epcoritamab for the tx of R/R FL.
Aims:
To assess MRD, PK, and PD of a 2-step SUD regimen in cycle (C) 1 in comparison with a 3-step optimization
regimen in C1 (C1 OPT) in patients with R/R FL.
Methods:
Patients with CD20+ R/R FL (grade 1–3A) with ≥2 prior tx lines received subcutaneous epcoritamab in 2-step
(0.16 and 0.8 mg) or 3-step (0.16, 0.8, and 3 mg) SUD regimens in C1, followed by 48-mg full doses in 28-day
(d) Cs (QW, C1–3; Q2W, C4–9; Q4W, C≥10) until disease progression. The C1 OPT cohort received
recommendations for adequate hydration and dexamethasone as the preferred steroid for CRS prophylaxis.
Hospitalization for monitoring was based on investigator discretion. T-cell phenotypes were assessed by
validated flow cytometry assays and cytokines were tested with the Meso Scale Discovery platform. MRD
analysis was performed on peripheral blood mononuclear cells collected at prespecified time points
(clonoSEQ® assay, Adaptive Biotechnologies). Screening tumor biopsies were used to identify trackable tumor
clones; samples were quantified as tumor clones detected per 1 million nucleated cells. Overall response and
progression-free survival (PFS) were assessed by Lugano criteria per investigator assessment.
Results:
PK was comparable between 2-step SUD and C1 OPT cohorts except for transient, lower epcoritamab trough
concentrations, as expected, after SUD 3 (3 mg) on C1D15 in the C1 OPT cohort compared with the 2-step SUD
cohort, which received the full dose (48 mg) on C1D15. The 2-step SUD cohort showed a marked increase in
median IL-6 levels 24 h after the first full dose on C1D15, whereas the C1 OPT cohort showed low median IL6
levels in C1 and beyond, supporting the reduction of CRS in the C1 OPT cohort. Rapid, sustained depletion of
circulating CD3−CD19+ peripheral B cells was observed by C1D15 in both groups. In addition, in both groups,
T-cell margination was observed in C1, followed by recovery to baseline levels by C2D1 and modest Tcell
expansion for subsequent doses. Frequency of proliferating Ki67+ and activated PD1+ CD4+ and CD8+ T cells
increased after each dose in C1 in both groups. T-cell proliferation and activation were prolonged to C2 in the
C1 OPT cohort. From C3 onward, the frequency of proliferating and activated T cells returned to near-baseline
levels and was similar in both groups. MRD negativity was observed in 61 (67%) of 91 evaluable patients in the
2-step SUD cohort and 28 (64%) of 44 patients in the C1 OPT cohort (Table). In the majority of durable
responders in both groups, epcoritamab induced MRD negativity by C3D1. In both groups, patients who lost
MRD-negative status also lost their response, and the majority of nonresponders never became MRD negative.
Median PFS was not reached in MRD-negative patients; for both dosing regimens, median PFS was around 4
mo for responders who were not MRD negative.
Summary/Conclusion:
MRD-negativity rate and kinetics, PK, longitudinal peripheral Bcell depletion, and T-cell counts were similar
between groups and consistent with comparable clinical efficacy reported for the C1 OPT and 2-step SUD
regimens. In contrast, IL-6 levels were substantially reduced for C1 OPT vs the 2-step SUD regimen.
Original languageEnglish
Publication statusPublished - Nov 2024
Event4th How to Diagnose and Treat Lymphoma is organized by European School of Haematology (ESH) - Clarion Hotel, Stockholm, Sweden
Duration: 1 Nov 20243 Nov 2024
https://www.esh.org/conference/4th-how-to-diagnose-and-treat-lymphoma/

Conference

Conference4th How to Diagnose and Treat Lymphoma is organized by European School of Haematology (ESH)
Country/TerritorySweden
CityStockholm
Period1/11/243/11/24
Internet address

Research Beacons, Institutes and Platforms

  • Cancer
  • Manchester Cancer Research Centre

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