Genmab and AbbVie Strengthen Epcoritamab’s Position in Follicular Lymphoma with Broad Subgroup Benefits from EPCORE FL-1
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Epcoritamab (E) plus Lenalidomide and Rituximab (R²) Demonstrates Consistent Benefit across Risk Groups in Relapsed/Refractory Follicular Lymphoma
Epcoritamab is a subcutaneous CD3×CD20 bispecific antibody co-developed by Genmab and AbbVie. The therapy has gained regulatory approvals across B-cell malignancies and recently received FDA approval in combination with rituximab and lenalidomide (R²) for patients with relapsed/refractory follicular lymphoma based on the positive Phase III EPCORE FL-1 trial. The current analysis evaluated whether the clinical benefit of E+R² was maintained across key patient subgroups, including FLIPI risk categories, POD24 status, comorbidity burden, and lenalidomide dose intensity. A total of 488 patients were enrolled, with 243 receiving E+R² and 238 receiving R².
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Efficacy Outcomes | ||||
|
Subgroup |
Treatment |
ORR (95% CI) |
CRR (95% CI) |
PFS HR (95% CI) for E+R²:R² |
|
Age ≥65 |
E+R² (n = 88) |
94.3 (87.2–98.1) |
80.7 (70.9–88.3) |
0.24 (0.13–0.44) |
|
R² (n = 106) |
80.2 (71.3–87.3) |
44.3 (34.7–54.3) | ||
|
Age <65 |
E+R² (n = 155) |
95.5 (90.9–98.2) |
83.9 (77.1–89.3) |
0.20 (0.12–0.33) |
|
R² (n = 139) |
78.4 (70.6–84.9) |
54.0 (45.3–62.4) | ||
|
FLIPI 0–2 |
E+R² (n = 142) |
96.5 (92.0–98.8) |
86.6 (79.9–91.7) |
0.18 (0.10–0.33) |
|
R² (n = 132) |
84.8 (77.6–90.5) |
62.1 (53.3–70.4) | ||
|
FLIPI 3–5 |
E+R² (n = 100) |
93.0 (86.1–97.1) |
77.0 (67.5–84.8) |
0.25 (0.15–0.42) |
|
R² (n = 113) |
72.6 (63.4–80.5) |
35.4 (26.6–45.0) | ||
|
NHL-5 Low |
E+R² (n = 166) |
94.0 (89.2–97.1) |
81.3 (74.6–86.9) |
0.27 (0.17–0.42) |
|
R² (n = 149) |
75.8 (68.2–82.5) |
50.3 (42.0–58.6) | ||
|
NHL-5 H+I |
E+R² (n = 77) |
97.4 (90.9–99.7) |
85.7 (75.9–92.6) |
0.14 (0.06–0.29) |
|
R² (n = 96) |
84.4 (75.5–91.0) |
49.0 (38.6–59.4) | ||
|
Non-POD24 |
E+R² (n = 131) |
96.2 (91.3–98.7) |
85.5 (78.3–91.0) |
0.17 (0.09–0.32) |
|
R² (n = 144) |
85.4 (78.6–90.7) |
57.6 (49.1–65.8) | ||
|
POD24 |
E+R² (n = 106) |
95.3 (89.3–98.5) |
80.2 (71.3–87.3) |
0.22 (0.13–0.37) |
|
R² (n = 93) |
69.9 (59.5–79.0) |
38.7 (28.8–49.4) | ||
|
1 Prior LOT |
E+R² (n = 145) |
95.9 (91.2–98.5) |
86.9 (80.3–91.9) |
0.20 (0.12–0.34) |
|
R² (n = 141) |
80.1 (72.6–86.4) |
53.2 (44.6–61.6) | ||
|
≥2 Prior LOT |
E+R² (n = 98) |
93.9 (87.1–97.7) |
76.5 (66.9–84.5) |
0.24 (0.13–0.42) |
|
R² (n = 97) |
77.9 (68.7–85.4) |
45.2 (35.4–55.3) | ||
|
Not Double Refractory |
E+R² (n = 152) |
95.4 (90.7–98.1) |
84.9 (78.2–90.2) |
0.19 (0.11–0.34) |
|
R² (n = 154) |
85.1 (78.4–90.3) |
58.4 (50.2–66.3) | ||
|
Double Refractory |
E+R² (n = 91) |
94.5 (87.6–98.2) |
79.1 (69.3–86.9) |
0.23 (0.13–0.39) |
|
R² (n = 91) |
69.2 (58.7–78.5) |
35.2 (25.4–45.9) | ||
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CRR: complete response rate; H+I: high and intermediate; HR: hazard ratio; LOT: line of therapy; ORR: overall response rate; FLIPI: Follicular Lymphoma International Prognostic Index; PFS: progression-free survival; POD24: progression of disease ≤2 years from the date of initiation of frontline therapy. | ||||
Safety Outcomes-
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Safety profile remained consistent across all evaluated subgroups.
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No new safety signals were identified.
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Adverse events were manageable and aligned with the overall EPCORE FL-1 study population.
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Treatment exposure remained consistent, with a median epcoritamab treatment duration of 10.4 months.
KOL Insights-
“There was a 79% reduction in the risk of disease progression or death. The epcoritamab combination led to sustained, improved efficacy with manageable safety across clinically relevant subgroups, consistent with the findings in the overall population.”– Expert Opinion
“Fixed-duration epcoritamab plus lenalidomide and rituximab was superior to lenalidomide and rituximab alone in the EPCORE FL-1 study among patients with FL in the second-line setting or later.” – Expert Opinion
Conclusion-
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma and remains characterized by repeated relapses despite advances in immunotherapy. Although R² and chemoimmunotherapy are established standards in relapsed disease, durable chemotherapy-free options capable of improving outcomes across diverse patient populations remain a significant unmet need.
The Phase III EPCORE FL-1 subgroup analysis demonstrated that E+R² consistently improved response rates, depth of response, and progression-free survival regardless of baseline disease risk, comorbidity burden, POD24 status, or lenalidomide dose intensity. These findings further strengthen the role of fixed-duration epcoritamab plus R² as a potential benchmark standard of care for a broad population of patients with relapsed/refractory follicular lymphoma.
Executive Summary
Subgroup analyses from the Phase III EPCORE FL-1 trial demonstrated that fixed-duration epcoritamab combined with lenalidomide and rituximab delivered consistent efficacy benefits across clinically relevant patient populations with R/R FL. Improvements in overall response rates (ORR), complete response (CR) rates, and progression-free survival (PFS) were observed irrespective of baseline risk features, disease fitness scores, POD24 status, or lenalidomide dose intensity, while maintaining a manageable safety profile.