A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma

Last updated: June 2, 2025
Sponsor: Genmab
Overall Status: Active - Recruiting

Phase

1/2

Condition

Hematologic Cancer

Lymphoma

White Cell Disorders

Treatment

CC-99282

Rituximab

Lenalidomide

Clinical Study ID

NCT05283720
M22-132
2021-005725-24
2023-505347-38
  • Ages > 18
  • All Genders

Study Summary

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cell (a white blood cell responsible for fighting infections). The purpose of this study is to assess the safety and tolerability of epcoritamab in combination with anti-neoplastic agents in adult participants with Non-Hodgkin lymphoma (NHL). Adverse events and change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of NHL. Study doctors put the participants in groups called treatment arms. The combination of epcoritamab with anti-neoplastic agents will be explored. Each treatment arm receives a different treatment combination depending on eligibility. Approximately 565 adult participants with NHL will be enrolled in 100 sites globally.

In both the dose escalation and dose expansion arms participants will receive subcutaneous (SC) epcoritamab in 28 day, 21 day, or 56 day cycles dependent on the arm in combination with the anti-neoplastic agents described below:

1: Oral lenalidomide in participants (PPTS) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL); 2: Oral ibrutinib and oral lenalidomide in PPTS with with R/R DLBCL; 3: Intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in PPTS with newly diagnosed treatment-naïve DLBCL; 4: Oral CC-99282 in PPTS with R/R DLBCL; 5: Oral CC-99282 in PPTS with R/R follicular lymphoma (FL); 6A: Oral ibrutinib in PPTS with R/R mantle cell lymphoma (MCL); 6B: Oral ibrutinib, and oral venetoclax in PPTS with R/R MCL; 7: Oral ibrutinib, and oral venetoclax in PPTS with newly diagnosed treatment-naïve MCL. 8: Oral pirtobrutinib in PPTS with R/R MCL.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Diagnosis of:

-- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed fromfollicular lymphoma (FL) or nodal marginal zone lymphoma) with histologicallyconfirmed CD20+ disease, inclusive of the following according to World HealthOrganization (WHO) 2016 classification and documented in pathology report:

  • DLBCL, not otherwise specified (NOS).

  • High-grade B cell lymphoma with MYC and BCL-2 and/or BCL-6 translocations perWHO 2016 ("double-hit" or "triple-hit") Note: High-grade B-cell lymphomas NOSor other double- /triple-hit lymphomas (with histologies not consistent withDLBCL) are not eligible.

  • Follicular lymphoma (FL) Grade 3B. OR

  • FL with histologically confirmed CD20+ Grade 1 to 3a and no evidence of histologictransformation to an aggressive lymphoma at most recent representative tumor biopsy,according to WHO 2016 classification. OR

  • Mantle cell lymphoma (MCL) with histologically confirmed CD20+ disease at mostrecent representative tumor biopsy according to the WHO 2016 classification withevidence of overexpression of cyclin D1 in association with relevant markers orevidence of t(11;14) assessed by flow cytometry, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR).

  • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, except for Arms 6, 7, and 8 where ECOG performance status must be 0-1.

  • Must have 1 or more measurable disease sites:

  • A positron emission tomography (PET) /computed tomography (CT) scandemonstrating PET-positive lesion(s) AND

  • At least 1 measurable nodal lesion (long axis > 1.5 cm) or >= 1 measurableextra-nodal lesion (long axis > 1.0 cm) on CT scan or magnetic resonanceimaging (MRI).

Exclusion

Exclusion Criteria:

  • Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 andCD20.

  • Toxicities from prior anticancer therapy that have not resolved to CommonTerminology Criteria for Adverse Events (CTCAE, v 5.0), Grade 2 or below, with theexception of alopecia. Other eligibility criteria (e.g., laboratory, cardiaccriteria) must also be met.

Study Design

Total Participants: 565
Treatment Group(s): 11
Primary Treatment: CC-99282
Phase: 1/2
Study Start date:
June 14, 2022
Estimated Completion Date:
November 30, 2032

Connect with a study center

  • BC Cancer - Vancouver /ID# 243946

    Vancouver, British Columbia V5Z 1L3
    Canada

    Site Not Available

  • Beijing Cancer Hospital /ID# 252303

    Beijing, Beijing 100142
    China

    Site Not Available

  • Fudan University Shanghai Cancer Center /Id# 252292

    Shanghai, Shanghai 200032
    China

    Site Not Available

  • Fakultní Nemocnice Brno - Jihlavská /ID# 242683

    Brno, Brno-mesto 625 00
    Czechia

    Active - Recruiting

  • Fakultní nemocnice Hradec Králové - Sokolská /ID# 241722

    Hradec Králové, Hradec Kralove 500 05
    Czechia

    Active - Recruiting

  • Fakultni Nemocnice Ostrava /ID# 242684

    Ostrava, Ostrava-mesto 708 52
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Hradec Kralove /ID# 241722

    Hradec Kralove, Praha 17 500 05
    Czechia

    Site Not Available

  • Fakultni Nemocnice Brno /ID# 242683

    Brno, 625 00
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Brno /ID# 242683

    Brno, 613 00
    Czechia

    Active - Recruiting

  • Fakultni nemocnice Ostrava /ID# 242684

    Ostrava, 708 52
    Czechia

    Site Not Available

  • Vseobecna fakultni nemocnice v Praze /ID# 242685

    Praha, 128 08
    Czechia

    Active - Recruiting

  • Aarhus Universitetshospital - Skejby /ID# 242670

    Aarhus, Midtjylland 8200
    Denmark

    Active - Recruiting

  • Aarhus University Hospital /ID# 242670

    Aarhus N, Midtjylland 8200
    Denmark

    Site Not Available

  • Aalborg University Hospital /ID# 242734

    Aalborg, Nordjylland 9000
    Denmark

    Active - Recruiting

  • CHU Clermont-Ferrand /ID# 242344

    Clermont, Auvergne-Rhone-Alpes 63100
    France

    Active - Recruiting

  • CHU de Rennes - PONTCHAILLOU /ID# 242339

    Rennes, Bretagne 35000
    France

    Active - Recruiting

  • Hopital Pitie Salpetriere /ID# 242343

    Paris, Ile-de-France 75013
    France

    Active - Recruiting

  • Institut de Recherche Saint Louis - Hopital St Louis /ID# 242336

    Paris, Ile-de-France 75010
    France

    Active - Recruiting

  • Hopital Pitie Salpetriere /ID# 242343

    Paris Cedex 13, Ile-de-France 75013
    France

    Active - Recruiting

  • CHRU Nancy - Hopitaux de Brabois /ID# 242342

    Vandoeuvre-les-Nancy, Meurthe-et-Moselle 54500
    France

    Active - Recruiting

  • CHRU Nancy - Hopitaux de Brabois /ID# 242342

    Vandœuvre-les-Nancy, Meurthe-et-Moselle 54500
    France

    Site Not Available

  • CHRU Nancy - Hôpitaux de Brabois /ID# 242342

    Vandœuvre-lès-Nancy, Meurthe-et-Moselle 54500
    France

    Site Not Available

  • CHRU Lille - Hopital Claude Huriez /ID# 242335

    Lille, Nord 59037
    France

    Active - Recruiting

  • IUCT Oncopole /ID# 242340

    Toulouse Cedex 9, Occitanie 31059
    France

    Active - Recruiting

  • Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 242337

    Creteil, Paris 94010
    France

    Active - Recruiting

  • CHU de Nantes, Hotel Dieu -HME /ID# 242345

    Nantes, Pays-de-la-Loire 44000
    France

    Active - Recruiting

  • HCL - Hopital Lyon Sud /ID# 242349

    Pierre Benite CEDEX, Rhone 69495
    France

    Active - Recruiting

  • Hopital Henri Mondor /ID# 242337

    Creteil, 94000
    France

    Site Not Available

  • Hôpitaux Universitaires Henri Mondor - Hôpital Henri Mondor /ID# 242337

    Créteil, 94010
    France

    Site Not Available

  • Hôpital Saint-Louis /ID# 242336

    Paris, 75010
    France

    Active - Recruiting

  • Universitaetsklinikum Ulm /ID# 244265

    Ulm, Baden-Wuerttemberg 89081
    Germany

    Active - Recruiting

  • Klinikum Augsburg /ID# 244523

    Augsburg, Bayern 86156
    Germany

    Active - Recruiting

  • Universitaetsklinikum Wuerzburg /ID# 245453

    Wuerzburg, Bayern 97080
    Germany

    Active - Recruiting

  • Universitaetsklinikum Giessen und Marburg /ID# 245308

    Marburg, Hessen 35043
    Germany

    Active - Recruiting

  • Universitaetsklinikum Muenster /ID# 248304

    Munster, Niedersachsen 48149
    Germany

    Site Not Available

  • Universitaetsklinikum Koeln /ID# 244521

    Köln, Nordrhein-Westfalen 50937
    Germany

    Site Not Available

  • Universitaetsklinikum Leipzig /ID# 245513

    Leipzig, Sachsen 04103
    Germany

    Active - Recruiting

  • Universitaetsklinikum Regensburg /ID# 244517

    Regensburg, 93042
    Germany

    Active - Recruiting

  • Universitaetsmedizin Rostock /ID# 244655

    Rostock, 18057
    Germany

    Site Not Available

  • Debreceni Egyetem Klinikai Kozpont /ID# 242450

    Debrecen, Hajdu-Bihar 4032
    Hungary

    Active - Recruiting

  • Debreceni Egyetem-Klinikai Kozpont /ID# 242450

    Debrecen, Hajdu-Bihar 4032
    Hungary

    Active - Recruiting

  • Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 245935

    Kaposvár, Somogy 7400
    Hungary

    Site Not Available

  • Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 245935

    Kaposvár, Somogy 7400
    Hungary

    Active - Recruiting

  • Orszagos Onkologiai Intezet /ID# 242458

    Budapest, 1122
    Hungary

    Active - Recruiting

  • Semmelweis Egyetem /ID# 242454

    Budapest, 1085
    Hungary

    Active - Recruiting

  • The Chaim Sheba Medical Center /ID# 243010

    Ramat Gan, Tel-Aviv 5265601
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Center /ID# 243012

    Tel Aviv, Tel-Aviv 6423906
    Israel

    Active - Recruiting

  • Tel Aviv Sourasky Medical Center /ID# 243012

    Tel Aviv-Yafo, Tel-Aviv 6423906
    Israel

    Site Not Available

  • Hadassah Medical Center-Hebrew University /ID# 243013

    Jerusalem, Yerushalayim 91120
    Israel

    Active - Recruiting

  • Rabin Medical Center /ID# 243014

    Haifa, 4941492
    Israel

    Site Not Available

  • Rabin Medical Center /ID# 243014

    Petah Tikva, 4941492
    Israel

    Active - Recruiting

  • Rabin Medical Center /ID# 243014

    Petakh Tikva, 4941492
    Israel

    Site Not Available

  • Hokkaido University Hospital /ID# 248999

    Sapporo-shi, Hokkaido 060-8648
    Japan

    Active - Recruiting

  • Kyoto University Hospital /ID# 248997

    Kyoto-shi, Kyoto 606-8507
    Japan

    Completed

  • National Cancer Center Hospital /ID# 248995

    Chuo-ku, Tokyo 104-0045
    Japan

    Active - Recruiting

  • Seoul National University Bundang Hospital /ID# 242404

    Seongnam, Gyeonggido 13620
    Korea, Republic of

    Site Not Available

  • Seoul National University Bundang Hospital /ID# 242404

    Seongnam-si, Gyeonggido 13620
    Korea, Republic of

    Active - Recruiting

  • Asan Medical Center /ID# 242400

    Seoul, Seoul Teugbyeolsi 05505
    Korea, Republic of

    Active - Recruiting

  • Samsung Medical Center /ID# 242401

    Seoul, Seoul Teugbyeolsi 06351
    Korea, Republic of

    Active - Recruiting

  • Seoul National University Hospital /ID# 242402

    Seoul, Seoul Teugbyeolsi 03080
    Korea, Republic of

    Active - Recruiting

  • The Catholic University of Korea, Seoul St. Marys Hospital /ID# 242403

    Seoul, Seoul Teugbyeolsi 06591
    Korea, Republic of

    Active - Recruiting

  • The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 242403

    Seoul, 06591
    Korea, Republic of

    Active - Recruiting

  • Maastricht Universitair Medisch Centrum /ID# 243317

    Maastricht, Limburg 6229 HX
    Netherlands

    Active - Recruiting

  • Vrije Universiteit Medisch Centrum /ID# 243319

    Amsterdam, Noord-Holland 1081 HV
    Netherlands

    Active - Recruiting

  • Leids Universitair Medisch Centrum /ID# 243316

    Leiden, Zuid-Holland 2333 ZA
    Netherlands

    Active - Recruiting

  • Duplicate_Erasmus Medisch Centrum /ID# 243315

    Rotterdam, Zuid-Holland 3015 GD
    Netherlands

    Completed

  • Erasmus Medisch Centrum /ID# 243315

    Rotterdam, Zuid-Holland 3015 GD
    Netherlands

    Completed

  • Universitair Medisch Centrum Groningen /ID# 243318

    Groningen, 9713 GZ
    Netherlands

    Active - Recruiting

  • Instituto Catalan de Oncologia (ICO) Badalona /ID# 243265

    Badalona, Barcelona 08916
    Spain

    Active - Recruiting

  • Instituto Catalan de Oncologia (ICO) L'Hospitalet /ID# 243261

    Hospitalet de Llobregat, Barcelona 08908
    Spain

    Site Not Available

  • Institut Català d'Oncologia (ICO) - L'Hospitalet /ID# 243261

    L'Hospitalet de Llobregat, Barcelona 08907
    Spain

    Active - Recruiting

  • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 245031

    Pamplona, Navarra 31008
    Spain

    Active - Recruiting

  • Clinica Universidad de Navarra - Pamplona /ID# 245031

    Pamplona, Navarra 31008
    Spain

    Active - Recruiting

  • Hospital Universitario Vall d'Hebron /ID# 243260

    Barcelona, 08035
    Spain

    Active - Recruiting

  • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 243268

    Madrid, 28027
    Spain

    Active - Recruiting

  • Hospital Universitario 12 de Octubre /ID# 243262

    Madrid, 28041
    Spain

    Active - Recruiting

  • Hospital Universitario Fundacion Jimenez Diaz /ID# 243264

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario La Paz /ID# 243266

    Madrid, 28046
    Spain

    Site Not Available

  • Hospital Universitario de Salamanca /ID# 243368

    Salamanca, 37711
    Spain

    Active - Recruiting

  • Duplicate_Hospital Universitario Virgen del Rocio /ID# 243267

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio /ID# 243267

    Sevilla, 41013
    Spain

    Active - Recruiting

  • Hospital Clinico Universitario de Valencia /ID# 243269

    Valencia, 46010
    Spain

    Active - Recruiting

  • China Medical University Hospital /ID# 242893

    Taichung, 40447
    Taiwan

    Active - Recruiting

  • China Medical University Hospital /ID# 242893

    Taichung City, 40447
    Taiwan

    Site Not Available

  • National Cheng Kung University Hospital /ID# 242894

    Tainan, 704
    Taiwan

    Active - Recruiting

  • Taipei Veterans General Hosp /ID# 242892

    Taipei, 11217
    Taiwan

    Active - Recruiting

  • Taipei Veterans General Hosp /ID# 242892

    Taipei City, 11217
    Taiwan

    Site Not Available

  • Leicester Royal Infirmary /ID# 246993

    Leicester, England LE1 5WW
    United Kingdom

    Site Not Available

  • Guys and St Thomas NHS Foundation Trust /ID# 245056

    London, London, City Of SE1 9RT
    United Kingdom

    Site Not Available

  • Imperial College Healthcare NHS Trust /ID# 245851

    London, W2 1NY
    United Kingdom

    Site Not Available

  • The Christie Hospital /ID# 243948

    Manchester, M20 4BX
    United Kingdom

    Site Not Available

  • The University of Arizona Cancer Center - North Campus /ID# 242219

    Tucson, Arizona 85719
    United States

    Active - Recruiting

  • University of Arizona Cancer Center - North Campus /ID# 242219

    Tucson, Arizona 85719-1478
    United States

    Active - Recruiting

  • Yale University /ID# 242089

    New Haven, Connecticut 06510
    United States

    Active - Recruiting

  • Yale University School of Medicine /ID# 242089

    New Haven, Connecticut 06510
    United States

    Active - Recruiting

  • Christiana Care Health Service /ID# 242301

    Newark, Delaware 19713
    United States

    Active - Recruiting

  • Tampa General Hospital /ID# 246748

    Tampa, Florida 33606
    United States

    Active - Recruiting

  • Emory University /ID# 242153

    Atlanta, Georgia 30322-1013
    United States

    Active - Recruiting

  • Winship Cancer Institute of Emory University /ID# 242153

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Augusta University Georgia Cancer Center /ID# 242140

    Augusta, Georgia 30912-0003
    United States

    Site Not Available

  • Southern IL Univ School of Med /ID# 242229

    Springfield, Illinois 62702
    United States

    Site Not Available

  • Norton Cancer Institute - St Matthews /ID# 242159

    Louisville, Kentucky 40207
    United States

    Site Not Available

  • University of Maryland Medical Center /ID# 242218

    Baltimore, Maryland 21201
    United States

    Active - Recruiting

  • University of Maryland School of Medicine /ID# 242218

    Baltimore, Maryland 21201-1544
    United States

    Active - Recruiting

  • University of Maryland, Baltimore /ID# 242218

    Baltimore, Maryland 21201
    United States

    Active - Recruiting

  • Alliance for Multispecialty Research (AMR) - Kansas City /ID# 242144

    Kansas City, Missouri 64114-4859
    United States

    Completed

  • Roswell Park Comprehensive Cancer Center /ID# 242129

    Buffalo, New York 14263
    United States

    Site Not Available

  • Northwell Health - Monter Cancer Center /ID# 245435

    Lake Success, New York 11042
    United States

    Active - Recruiting

  • Icahn School of Medicine at Mount Sinai /ID# 242123

    New York, New York 10029
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 242305

    New York, New York 10065-6007
    United States

    Site Not Available

  • Novant Health Presbyterian Medical Center /ID# 242148

    Charlotte, North Carolina 28204
    United States

    Active - Recruiting

  • East Carolina University - Brody School of Medicine /ID# 242506

    Greenville, North Carolina 27834
    United States

    Active - Recruiting

  • East Carolina University Brody School of Medicine /ID# 242506

    Greenville, North Carolina 27834
    United States

    Active - Recruiting

  • Novant Health Forsyth Medical Center /ID# 242198

    Winston-Salem, North Carolina 27103
    United States

    Active - Recruiting

  • Gabrail Cancer Center Research /ID# 242212

    Canton, Ohio 44718
    United States

    Site Not Available

  • Fox Chase Cancer Center /ID# 242106

    Philadelphia, Pennsylvania 19111
    United States

    Completed

  • Thomas Jefferson University /ID# 242077

    Philadelphia, Pennsylvania 19107-4414
    United States

    Active - Recruiting

  • Thomas Jefferson University Hospital /ID# 242077

    Philadelphia, Pennsylvania 19107
    United States

    Completed

  • Lankenau Medical Center /ID# 242124

    Wynnewood, Pennsylvania 19096
    United States

    Site Not Available

  • Medical University of South Carolina /ID# 242059

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Thompson Cancer Survival Ctr /ID# 242150

    Knoxville, Tennessee 37916
    United States

    Completed

  • Joe Arrington Cancer Research /ID# 242226

    Lubbock, Texas 79410
    United States

    Completed

  • Swedish Cancer Institute - First Hill /ID# 242269

    Seattle, Washington 98104
    United States

    Active - Recruiting

  • Swedish Cancer Institute /ID# 242269

    Seattle, Washington 98104-3588
    United States

    Active - Recruiting

  • Swedish Cancer Institute- First Hill /ID# 242269

    Seattle, Washington 98104
    United States

    Active - Recruiting

  • MultiCare Institute for Research & Innovation /ID# 242127

    Tacoma, Washington 98405
    United States

    Active - Recruiting

  • Multicare Institute for Research and Innovation /ID# 242127

    Tacoma, Washington 98405
    United States

    Active - Recruiting

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