CONTEXT: R/R FL is associated with a poor prognosis and remains incurable; thus, better treatment options are needed. Epcoritamab is a subcutaneously administered CD3xCD20 bispecific antibody that has shown substantial antitumor activity in R/R FL. OBJECTIVE: Evaluate safety and efficacy of epcoritamab with R2 in patients with R/R FL in arm 2 of a phase 1/2 open-label trial (EPCORE NHL-2; NCT04663347). PATIENTS: Adults with R/R CD20+ FL were included. As of December 1, 2021, 30 patients (median age, 68 y) had enrolled. INTERVENTIONS: Patients received subcutaneous epcoritamab (QW, cycle [C] 1-3; Q2W, C4-9; Q4W, C≥10 up to 2 y) + R2 for 12 cycles of 28 d. Step-up dosing and corticosteroid prophylaxis were required. RESULTS: Of the 30 patients (epcoritamab 24 mg, n=3; 48 mg, n=27), 21 (70%) had stage IV disease and 20 (67%) had FLIPI scores 3-5. Median (range) number of prior lines of therapy was 1 (1-5), 30% had primary refractory disease, and 40% had disease progression within 24 mo after starting first-line treatment. At a median (range) follow-up of 5.1 mo (0.8-12.3), 25 patients (83%) remained on treatment; 5 patients discontinued treatment due to progression (n=2), AEs (n=2), or consent withdrawal (n=1). Common treatment-emergent AEs (TEAEs) of any grade (G) included infections (57%), injection-site reactions (50%), constipation (37%), fatigue (37%), and neutropenia (37%). CRS events occurred in 15 patients (50%; G1-2 43%, G3 7%), primarily in C1. All CRS events resolved; 3 patients were treated with tocilizumab, and 1 patient discontinued treatment due to CRS. One patient experienced G2 ICANS. No fatal TEAEs occurred. Overall response rate for the 27 evaluable patients was 100%; 93% had a complete metabolic response (CMR) and 7% had a partial metabolic response by PET-CT. As of the data cut, the longest duration of response was 7.0+ mo and ongoing. CONCLUSIONS: Subcutaneous epcoritamab + R2 exhibits promising efficacy, including a high CMR rate, in patients with R/R FL. The safety profile was consistent with prior data. Updated data will be presented. FUNDING: This study was funded by Genmab A/S and AbbVie.

• MeSH
• dospělí MeSH
• folikulární lymfom * farmakoterapie   patologie   MeSH
• lenalidomid terapeutické užití   MeSH
• lidé MeSH
• PET/CT MeSH
• protilátky bispecifické terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie * škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH

CONTEXT: Patients with newly diagnosed high-risk DLBCL have suboptimal outcomes. Subcutaneous epcoritamab is a CD3xCD20 bispecific antibody well suited for combination with standard of care therapies. OBJECTIVE: Evaluate safety and efficacy of epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated patients with high-risk DLBCL in arm 1 of a phase 1/2, open-label trial (EPCORE NHL-2; NCT04663347). PATIENTS: Adults with previously untreated CD20+ DLBCL and IPI ≥3 were included. As of December 1, 2021, 33 patients (median age, 66 y) had enrolled. INTERVENTIONS: Patients received subcutaneous epcoritamab (QW, cycles 1-4; Q3W, cycles 5-6) + R-CHOP for 6 cycles (21 d) followed by epcoritamab monotherapy Q4W up to 1 y (in cycles of 28 d). Step-up dosing and corticosteroid prophylaxis were required. RESULTS: All 33 patients treated (epcoritamab 24 mg, n=4; 48 mg, n=29) had IPI ≥3, and ≥24% had double/triple-hit DLBCL. Median follow-up was 3 mo (range, 0-9.7), median number of total cycles initiated was 5 (1-13), and 94% of patients (31/33) remained on treatment. Treatment-emergent AEs (TEAEs) in ≥35% of patients were neutropenia (48%; febrile neutropenia in 9% of all patients), CRS (45%), infections (42%), anemia (39%), and injection-site reactions (36%). No TEAEs led to epcoritamab discontinuation. Most CRS events were low grade (42% grade [G] 1-2, 3% G3), occurred in cycle 1, and resolved after a median of 2 d (1-11); 4 patients received tocilizumab. G2 ICANS occurred in 1 patient. No fatal TEAEs occurred. In efficacy-evaluable patients, the overall response rate (ORR) was 96% (24/25); 68% (17/25) had complete metabolic response (CMR) by PET-CT. In the 10 patients who completed 6 cycles of R-CHOP by the cutoff date, ORR and CMR rate were 100% and 90%, respectively; all patients remained in response at data cutoff (longest duration of response, 7.1+ mo, ongoing). CONCLUSIONS: Epcoritamab + R-CHOP had manageable safety, mostly low-grade CRS that did not lead to treatment discontinuation, and high response rates in patients with previously untreated DLBCL. Updated data will be presented. FUNDING: This study was funded by Genmab A/S and AbbVie.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• difúzní velkobuněčný B-lymfom * farmakoterapie   patologie   MeSH
• dospělí MeSH
• doxorubicin terapeutické užití   MeSH
• lidé MeSH
• PET/CT MeSH
• prednison terapeutické užití   MeSH
• protilátky bispecifické terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie * škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• vinkristin terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH