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PRIMARY RESULTS OF SUBCUTANEOUS EPCORITAMAB DOSE EXPANSION IN PATIENTS WITH RELAPSED OR REFRACTORY LARGE B-CELL LYMPHOMA: A PHASE 2 STUDY
Author(s): ,
Catherine Thieblemont
Affiliations:
Assistance Publique & Hôpitaux de Paris (APHP),Paris,France;Hôpital Saint-Louis, Hémato-oncologie, Université de Paris,Paris,France
,
Tycel Phillips
Affiliations:
University of Michigan Comprehensive Cancer Center,Ann Arbor, MI,United States
,
Herve Ghesquieres
Affiliations:
Hospices Civils de Lyon Centre, Hospitalier Lyon Sud,Pierre-Bénite,France
,
Chan Y. Cheah
Affiliations:
Sir Charles Gairdner Hospital,Nedlands,Australia
,
Michael Roost Clausen
Affiliations:
Vejle Hospital,Vejle,Denmark
,
David Cunningham
Affiliations:
The Royal Marsden NHS Foundation Trust,Sutton,United Kingdom
,
Young Rok Do
Affiliations:
Keimyung University Dongsan Medical Center,Daegu,Korea, Republic Of
,
Tatyana Feldman
Affiliations:
Hackensack Meridian Health Hackensack University Medical Center,Hackensack, NJ,United States
,
Robin Gasiorowski
Affiliations:
Concord Hospital, University of Sydney,Sydney,Australia
,
Wojciech Jurczak
Affiliations:
MSC National Research Institute of Oncology,Kraków,Poland
,
Tae Min Kim
Affiliations:
Seoul National University Hospital,Seoul,Korea, Republic Of
,
David John Lewis
Affiliations:
University Hospitals Plymouth NHS Trust, Derriford Hospital,Plymouth,United Kingdom
,
Marjolein van der Poel
Affiliations:
On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC,Maastricht,Netherlands;Department of Internal Medicine, Division of Hematology,GROW School for Oncology and Developmental Biology, Maastricht University Medical Center,Maastricht,Netherlands
,
Michelle Limei Poon
Affiliations:
National University Hospital,Kent Ridge,Singapore
,
Thomas Doerr
Affiliations:
AbbVie,North Chicago, IL,United States
,
Nurgul Kilavuz
Affiliations:
Genmab,Princeton, NJ,United States
,
Menghui Chen
Affiliations:
Genmab,Princeton, NJ,United States
,
Mariana Sacchi
Affiliations:
Genmab,Princeton, NJ,United States
,
Brian Elliott
Affiliations:
Genmab,Princeton, NJ,United States
,
Martin Hutchings
Affiliations:
Rigshospitalet, Copenhagen University Hospital,Copenhagen,Denmark
Pieternella Lugtenburg
Affiliations:
On behalf of the Lunenburg Lymphoma Phase I/II Consortium-HOVON/LLPC,Rotterdam,Netherlands;Department of Hematology,Erasmus MC Cancer Institute, University Medical Center,Rotterdam,Netherlands
(Abstract release date: 06/12/22) EHA Library. Thieblemont C. 06/11/22; 366208; LB2364
Catherine Thieblemont
Catherine Thieblemont
Contributions
Abstract
Presentation during EHA2022: The Presidential Symposium will be held on Saturday, June 11, 2022 (14:45 - 16:15 CEST) and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: LB2364

Type: Late breaking presidential

Session title: Presidential Symposium

Background
Recently, multiple therapies have emerged with novel mechanisms of action, but an unmet need remains for more tolerable and readily available treatment options that can induce deep and durable responses in patients (pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Epcoritamab is a novel, subcutaneous (SC) CD3/CD20 bispecific antibody that has shown preliminary potent antitumor activity across B-cell NHL subtypes in dose escalation as a single agent and in combination with various standards of care. 

Aims
We report primary results from the LBCL expansion cohort in the phase 2 study of SC epcoritamab in pts with R/R B-cell NHL (EPCORE NHL-1; NCT03625037).

Methods
Adults with R/R CD20+ LBCL received epcoritamab (priming and intermediate doses followed by full doses of 48 mg) as 1-mL SC injections in cycles (C) of 28 days (QW: C1–3; Q2W: C4–9; Q4W C≥10) until disease progression or unacceptable toxicity. CRS mitigation included step-up dosing and corticosteroid prophylaxis (C1 only). Per protocol, 24-h hospitalization was only required for the first full dose to ensure close observation of the pts. Informed consent was obtained.

Results
As of Jan 31, 2022, 157 pts with DLBCL (including double/triple-hit and transformed), high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), or follicular lymphoma (FL) grade 3B were treated. Median age was 64 y (range, 20–83) with 49.0% 65 y and 18.5% 75 y. Pts had a median of 3 (range, 2–11) prior lines of therapy (LOT) and a median of 1.6 y from initial diagnosis. Notably, 61 pts (38.9%) received prior CAR T (75% of those progressed within 6 mo of CAR T) and 31 (19.7%) had prior ASCT (58% of those progressed within 12 mo of ASCT). Overall, 61% had primary refractory disease, and 83% were refractory to the last LOT. At a median follow-up of 10.7 mo, the overall response rate (ORR) by IRC based on Lugano criteria and assessed by PET-CT was 63% with 39% complete response (CR); see Figure. The ORR/CR rates were 69%/42% for CAR T–naive pts and 54%/34% for pts with prior CAR T. The median duration of response (mDOR) was 12 mo, while the mDOR among pts achieving CR was not reached, with 89% still in CR at 9 mo (KM estimate). ORR was similar across prespecified subgroups of age, prior LOT, and de novo or transformed disease. The most common treatment-emergent AEs (TEAEs) of any grade were cytokine release syndrome (CRS; 49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), and diarrhea (20.4%). Twelve pts (7.6%) had TEAEs that led to treatment discontinuation; 3 were considered treatment related (CRS, worsening CLIPPERS, and ICANS). Incidence of CRS events was: G1 31.8%, G2 15.3%, and G3 2.5%; events occurred mainly following the first full dose on C1D15 (median onset 20 h after SC injection; median time to resolution 48 h). Overall, 22 pts (14%) received tocilizumab. Ten pts (6.4%) experienced ICANS; all but one event was G1/2, and G5 ICANS was the only treatment-related death.

Conclusion
Epcoritamab is a convenient, SC, off-the-shelf therapy that demonstrated clinically meaningful and compelling efficacy including deep and durable responses in a challenging to treat, highly refractory LBCL population. While efficacy was observed in both CAR T–exposed and CAR T–naive pts, a numerically higher percentage of CAR T–naive pts responded to single-agent epcoritamab. The safety profile was manageable and consistent with previous findings. Notably, most CRS events were low grade and occurred during C1, ICANS was limited, and there were few discontinuations due to AEs.

Keyword(s): Bispecific, Diffuse large B cell lymphoma, Hematological malignancy, Non-Hodgkin's lymphoma

Presentation during EHA2022: The Presidential Symposium will be held on Saturday, June 11, 2022 (14:45 - 16:15 CEST) and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: LB2364

Type: Late breaking presidential

Session title: Presidential Symposium

Background
Recently, multiple therapies have emerged with novel mechanisms of action, but an unmet need remains for more tolerable and readily available treatment options that can induce deep and durable responses in patients (pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Epcoritamab is a novel, subcutaneous (SC) CD3/CD20 bispecific antibody that has shown preliminary potent antitumor activity across B-cell NHL subtypes in dose escalation as a single agent and in combination with various standards of care. 

Aims
We report primary results from the LBCL expansion cohort in the phase 2 study of SC epcoritamab in pts with R/R B-cell NHL (EPCORE NHL-1; NCT03625037).

Methods
Adults with R/R CD20+ LBCL received epcoritamab (priming and intermediate doses followed by full doses of 48 mg) as 1-mL SC injections in cycles (C) of 28 days (QW: C1–3; Q2W: C4–9; Q4W C≥10) until disease progression or unacceptable toxicity. CRS mitigation included step-up dosing and corticosteroid prophylaxis (C1 only). Per protocol, 24-h hospitalization was only required for the first full dose to ensure close observation of the pts. Informed consent was obtained.

Results
As of Jan 31, 2022, 157 pts with DLBCL (including double/triple-hit and transformed), high-grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), or follicular lymphoma (FL) grade 3B were treated. Median age was 64 y (range, 20–83) with 49.0% 65 y and 18.5% 75 y. Pts had a median of 3 (range, 2–11) prior lines of therapy (LOT) and a median of 1.6 y from initial diagnosis. Notably, 61 pts (38.9%) received prior CAR T (75% of those progressed within 6 mo of CAR T) and 31 (19.7%) had prior ASCT (58% of those progressed within 12 mo of ASCT). Overall, 61% had primary refractory disease, and 83% were refractory to the last LOT. At a median follow-up of 10.7 mo, the overall response rate (ORR) by IRC based on Lugano criteria and assessed by PET-CT was 63% with 39% complete response (CR); see Figure. The ORR/CR rates were 69%/42% for CAR T–naive pts and 54%/34% for pts with prior CAR T. The median duration of response (mDOR) was 12 mo, while the mDOR among pts achieving CR was not reached, with 89% still in CR at 9 mo (KM estimate). ORR was similar across prespecified subgroups of age, prior LOT, and de novo or transformed disease. The most common treatment-emergent AEs (TEAEs) of any grade were cytokine release syndrome (CRS; 49.7%), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), and diarrhea (20.4%). Twelve pts (7.6%) had TEAEs that led to treatment discontinuation; 3 were considered treatment related (CRS, worsening CLIPPERS, and ICANS). Incidence of CRS events was: G1 31.8%, G2 15.3%, and G3 2.5%; events occurred mainly following the first full dose on C1D15 (median onset 20 h after SC injection; median time to resolution 48 h). Overall, 22 pts (14%) received tocilizumab. Ten pts (6.4%) experienced ICANS; all but one event was G1/2, and G5 ICANS was the only treatment-related death.

Conclusion
Epcoritamab is a convenient, SC, off-the-shelf therapy that demonstrated clinically meaningful and compelling efficacy including deep and durable responses in a challenging to treat, highly refractory LBCL population. While efficacy was observed in both CAR T–exposed and CAR T–naive pts, a numerically higher percentage of CAR T–naive pts responded to single-agent epcoritamab. The safety profile was manageable and consistent with previous findings. Notably, most CRS events were low grade and occurred during C1, ICANS was limited, and there were few discontinuations due to AEs.

Keyword(s): Bispecific, Diffuse large B cell lymphoma, Hematological malignancy, Non-Hodgkin's lymphoma

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