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

NCT05283720 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: M22-1322023-505347-382023-505347-38-00
• Study Type: interventional
• Target: 496
• Locations: 13 countries
• Sites: 76

Brief 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 496 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 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, or completion of treatment in 3B; 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). 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.

Conditions

Non-Hodgkin Lymphoma

Keywords

Non-Hodgkin Lymphoma; Epcoritamab; Lenalidomide; Ibrutinib; Polatuzumab Vedotin; Rituximab; Cyclophosphamide; Doxorubicin Hydrochloride (HCl]; Prednisone (pola-R-CHP); ABBV-GMAB-3013; Cancer; Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL), Venetoclax,; Venclexta; ABT-199; GDC-0199; CC-99282; EPCORE; Pirtobrutinib; Mantle Cell Lymhoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose-Limiting Toxicities (DLT)

  DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.

  Up to Approximately 5 Years

Secondary Outcomes (8)

• Best Overall Response (BOR) per Investigator

  Up to Approximately 5 Years

• Duration of response (DOR) per Investigator

  Up to Approximately 5 Years

• Number of Participants with Progression-free survival (PFS)

  Up to Approximately 5 Years

• Percentage of Participants with Complete Response (CR)

  Up to Approximately 5 Years

• Time-to-response (TTR)

  Up to Approximately 5 Years

Study Arms (13)

Arm 1: Dose Escalation

EXPERIMENTAL

Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of epcoritamab in combination with lenalidomide in 28 day cycles.

Drug: Epcoritamab; Drug: Lenalidomide

Arm 2: Dose Escalation

EXPERIMENTAL

Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with ibrutinib and lenalidomide in 28 day cycles.

Drug: Epcoritamab; Drug: Lenalidomide; Drug: Ibrutinib

Arm 3: Dose Escalation

EXPERIMENTAL

Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.

Drug: Epcoritamab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride [HCl]; Drug: Prednisone; Drug: Polatuzumab Vedotin

Arm 4: Dose Escalation

EXPERIMENTAL

Participants with R/R DLBCL will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.

Drug: Epcoritamab; Drug: CC-99282

Arm 5: Dose Escalation

EXPERIMENTAL

Participants with R/R follicular lymphoma (FL) will receive escalating doses of epcoritamab in combination with CC-99282 in 28 day cycles.

Drug: Epcoritamab; Drug: CC-99282

Arm 6A: Dose Escalation

EXPERIMENTAL

Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of epcoritamab in combination with ibrutinib in 28 day cycles.

Drug: Epcoritamab; Drug: Ibrutinib

Arm 1: Dose Expansion

EXPERIMENTAL

Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with lenalidomide in 28 day cycles.

Drug: Epcoritamab; Drug: Lenalidomide

Arm 2: Dose Expansion

EXPERIMENTAL

Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.

Drug: Epcoritamab; Drug: Lenalidomide; Drug: Ibrutinib

Arm 3: Dose Expansion

EXPERIMENTAL

Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP) in 21 day cycles.

Drug: Epcoritamab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride [HCl]; Drug: Prednisone; Drug: Polatuzumab Vedotin

Arm 3B: Dose Expansion

EXPERIMENTAL

Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of epcoritamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin hydrochloride (HCl), and prednisone (pola-R-CHP), in 21 day cycles,until unacceptable toxicity, withdrawal of consent, or completion of treatment.

Drug: Epcoritamab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride [HCl]; Drug: Prednisone; Drug: Polatuzumab Vedotin

Arm 4: Dose Expansion

EXPERIMENTAL

Participants with R/R DLBCL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.

Drug: Epcoritamab; Drug: CC-99282

Arm 5: Dose Expansion

EXPERIMENTAL

Participants with R/R FL will receive the recommended dose of epcoritamab in combination with CC-99282 in 28 day cycles.

Drug: Epcoritamab; Drug: CC-99282

Arm 6: Dose Expansion

EXPERIMENTAL

Participants with R/R MCL will receive the recommended dose of epcoritamab in combination with ibrutinib in 28 day cycles.

Drug: Epcoritamab; Drug: Ibrutinib

Interventions

Epcoritamab DRUG

Subcutaneous Injection (SC)

Also known as: ABBV-GMAB-3013;

Arm 1: Dose Escalation; Arm 1: Dose Expansion; Arm 2: Dose Escalation; Arm 2: Dose Expansion; Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion; Arm 4: Dose Escalation; Arm 4: Dose Expansion; Arm 5: Dose Escalation; Arm 5: Dose Expansion; Arm 6: Dose Expansion; Arm 6A: Dose Escalation

Lenalidomide DRUG

Oral; Capsule

Arm 1: Dose Escalation; Arm 1: Dose Expansion; Arm 2: Dose Escalation; Arm 2: Dose Expansion

Ibrutinib DRUG

Oral; Capsule

Also known as: Imbruvica

Arm 2: Dose Escalation; Arm 2: Dose Expansion; Arm 6: Dose Expansion; Arm 6A: Dose Escalation

Rituximab DRUG

Intravenous (IV); Injection

Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion

Cyclophosphamide DRUG

IV; Injection

Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion

Doxorubicin Hydrochloride [HCl] DRUG

IV; Injection

Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion

Prednisone DRUG

Oral; Tablet

Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion

Polatuzumab Vedotin DRUG

IV; Injection

Arm 3: Dose Escalation; Arm 3: Dose Expansion; Arm 3B: Dose Expansion

CC-99282 DRUG

Oral; Capsule

Arm 4: Dose Escalation; Arm 4: Dose Expansion; Arm 5: Dose Escalation; Arm 5: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of:
• \-- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma (FL) or nodal marginal zone lymphoma) with histologically confirmed CD20+ disease, inclusive of the following according to World Health Organization (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 per WHO 2016 ("double-hit" or "triple-hit") Note: High-grade B-cell lymphomas NOS or other double- /triple-hit lymphomas (with histologies not consistent with DLBCL) are not eligible.
• Follicular lymphoma (FL) Grade 3B. OR
• FL with histologically confirmed CD20+ Grade 1 to 3a and no evidence of histologic transformation 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 most recent representative tumor biopsy according to the WHO 2016 classification with evidence of overexpression of cyclin D1 in association with relevant markers or evidence 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 Arm 6A where ECOG performance status must be 0-1.
• Must have 1 or more measurable disease sites:
• A positron emission tomography (PET) /computed tomography (CT) scan demonstrating PET-positive lesion(s) AND
• At least 1 measurable nodal lesion (long axis \> 1.5 cm) or \>= 1 measurable extra-nodal lesion (long axis \> 1.0 cm) on CT scan or magnetic resonance imaging (MRI).

You may not qualify if:

• Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20.
• Toxicities from prior anticancer therapy that have not resolved to Common Terminology Criteria for Adverse Events (CTCAE, v 5.0), Grade 2 or below, with the exception of alopecia. Other eligibility criteria (e.g., laboratory, cardiac criteria) must also be met.

Sponsors & Collaborators

• Genmab: lead
• AbbVie: collaborator

Study Sites (76)

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

Tucson, Arizona, 85719, United States

COMPLETED

Yale University School of Medicine /ID# 242089

New Haven, Connecticut, 06510, United States

RECRUITING

Christiana Care Health Service /ID# 242301

Newark, Delaware, 19713, United States

RECRUITING

Tampa General Hospital /ID# 246748

Tampa, Florida, 33606, United States

RECRUITING

Winship Cancer Institute of Emory University /ID# 242153

Atlanta, Georgia, 30322, United States

COMPLETED

University of Maryland, Baltimore /ID# 242218

Baltimore, Maryland, 21201, United States

RECRUITING

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

Kansas City, Missouri, 64114-4859, United States

COMPLETED

Northwell Health - Monter Cancer Center /ID# 245435

Lake Success, New York, 11042, United States

RECRUITING

Icahn School of Medicine at Mount Sinai /ID# 242123

New York, New York, 10029, United States

RECRUITING

Novant Health Presbyterian Medical Center /ID# 242148

Charlotte, North Carolina, 28204, United States

COMPLETED

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

Greenville, North Carolina, 27834, United States

RECRUITING

Novant Health Forsyth Medical Center /ID# 242198

Winston-Salem, North Carolina, 27103, United States

COMPLETED

Thomas Jefferson University Hospital /ID# 242077

Philadelphia, Pennsylvania, 19107, United States

COMPLETED

Fox Chase Cancer Center /ID# 242106

Philadelphia, Pennsylvania, 19111, United States

COMPLETED

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 Medical Center - Seattle /ID# 242269

Seattle, Washington, 98104, United States

RECRUITING

MultiCare Institute for Research & Innovation /ID# 242127

Tacoma, Washington, 98405, United States

COMPLETED

Beijing Cancer Hospital /ID# 252303

Beijing, Beijing Municipality, 100142, China

RECRUITING

Fudan University Cancer Hospital /ID# 252292

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Fakultni Nemocnice Brno - Jihlavska /ID# 242683

Brno, Brno-mesto, 625 00, Czechia

RECRUITING

Fakultní nemocnice Hradec Králové - Sokolská /ID# 241722

Hradec Králové, Hradec Kralove, 500 05, Czechia

RECRUITING

Fakultni Nemocnice Ostrava /ID# 242684

Ostrava, Ostrava-mesto, 708 52, Czechia

RECRUITING

Vseobecna Fakultni nemocnice v Praze /ID# 242685

Prague, Praha 17, 128 00, Czechia

RECRUITING

Aarhus Universitetshospital - Skejby /ID# 242670

Aarhus, Central Jutland, 8200, Denmark

RECRUITING

Aalborg University Hospital /ID# 242734

Aalborg, North Denmark, 9000, Denmark

COMPLETED

CHU Clermont-Ferrand /ID# 242344

Clermont, Auvergne-Rhône-Alpes, 63100, France

RECRUITING

CHU de Rennes - PONTCHAILLOU /ID# 242339

Rennes, Brittany Region, 35000, France

RECRUITING

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois /ID# 242342

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France

RECRUITING

CHRU Lille - Hopital Claude Huriez /ID# 242335

Lille, Nord, 59037, France

COMPLETED

IUCT Oncopole /ID# 242340

Toulouse, Occitanie, 31059, France

COMPLETED

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

Créteil, Paris, 94010, France

RECRUITING

Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 242345

Nantes, Pays de la Loire Region, 44000, France

RECRUITING

HCL - Hopital Lyon Sud /ID# 242349

Pierre-Bénite, Rhone, 69495, France

RECRUITING

Hopital Saint-Louis /ID# 242336

Paris, 75010, France

RECRUITING

Hopital Pitie Salpetriere /ID# 242343

Paris, Île-de-France Region, 75013, France

RECRUITING

Universitaetsklinikum Ulm /ID# 244265

Ulm, Baden-Wurttemberg, 89081, Germany

RECRUITING

Klinikum Augsburg /ID# 244523

Augsburg, Bavaria, 86156, Germany

RECRUITING

Universitaetsklinikum Regensburg /ID# 244517

Regensburg, Bavaria, 93042, Germany

RECRUITING

Universitaetsklinikum Wuerzburg /ID# 245453

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitaetsklinikum Giessen und Marburg /ID# 245308

Marburg, Hesse, 35043, Germany

COMPLETED

Universitaetsklinikum Leipzig /ID# 245513

Leipzig, Saxony, 04103, Germany

RECRUITING

Debreceni Egyetem-Klinikai Kozpont /ID# 242450

Debrecen, Hajdú-Bihar, 4032, Hungary

RECRUITING

Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 245935

Kaposvár, Somogy County, 7400, Hungary

RECRUITING

Semmelweis Egyetem /ID# 242454

Budapest, 1085, Hungary

RECRUITING

Orszagos Onkologiai Intezet /ID# 242458

Budapest, 1122, Hungary

RECRUITING

Rabin Medical Center. /ID# 243014

Petah Tikva, Central District, 4941492, Israel

RECRUITING

Hadassah Medical Center-Hebrew University /ID# 243013

Jerusalem, Jerusalem, 91120, Israel

RECRUITING

The Chaim Sheba Medical Center /ID# 243010

Ramat Gan, Tel Aviv, 5265601, Israel

RECRUITING

Tel Aviv Sourasky Medical Center /ID# 243012

Tel Aviv, Tel Aviv, 6423906, Israel

RECRUITING

Hokkaido University Hospital /ID# 248999

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Kyoto University Hospital /ID# 248997

Kyoto, Kyoto, 606-8507, Japan

COMPLETED

National Cancer Center Hospital /ID# 248995

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Maastricht Universitair Medisch Centrum /ID# 243317

Maastricht, Limburg, 6229 HX, Netherlands

COMPLETED

Vrije Universiteit Medisch Centrum /ID# 243319

Amsterdam, North Holland, 1081 HV, Netherlands

RECRUITING

Leids Universitair Medisch Centrum /ID# 243316

Leiden, South Holland, 2333 ZA, Netherlands

COMPLETED

Duplicate_Erasmus Medisch Centrum /ID# 243315

Rotterdam, South Holland, 3015 GD, Netherlands

COMPLETED

Universitair Medisch Centrum Groningen /ID# 243318

Groningen, 9713 GZ, Netherlands

COMPLETED

Seoul National University Bundang Hospital /ID# 242404

Seongnam-si, Gyeonggido, 13620, South Korea

RECRUITING

Seoul National University Hospital /ID# 242402

Seoul, Seoul Teugbyeolsi, 03080, South Korea

RECRUITING

Asan Medical Center /ID# 242400

Seoul, Seoul Teugbyeolsi, 05505, South Korea

RECRUITING

Samsung Medical Center /ID# 242401

Seoul, Seoul Teugbyeolsi, 06351, South Korea

RECRUITING

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

Seoul, Seoul Teugbyeolsi, 06591, South Korea

RECRUITING

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

Badalona, Barcelona, 08916, Spain

RECRUITING

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

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Clinica Universidad de Navarra - Pamplona /ID# 245031

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitario Vall de Hebron /ID# 243260

Barcelona, 08035, Spain

RECRUITING

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 243268

Madrid, 28027, Spain

RECRUITING

Hospital Universitario Fundacion Jimenez Diaz /ID# 243264

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre /ID# 243262

Madrid, 28041, Spain

RECRUITING

Hospital Universitario de Salamanca /ID# 243368

Salamanca, 37711, Spain

RECRUITING

Hospital Universitario Virgen del Rocio /ID# 243267

Seville, 41013, Spain

RECRUITING

Hospital Clinico Universitario de Valencia /ID# 243269

Valencia, 46010, Spain

RECRUITING

China Medical University Hospital /ID# 242893

Taichung, 40447, Taiwan

RECRUITING

National Cheng Kung University Hospital /ID# 242894

Tainan, 704, Taiwan

RECRUITING

Taipei Veterans General Hosp /ID# 242892

Taipei, 11217, Taiwan

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Hairy Cell; Neoplasms; Recurrence; Lymphoma, Large B-Cell, Diffuse

Interventions

Lenalidomide; ibrutinib; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia; Hematologic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2022
• First Posted: March 17, 2022
• Study Start: June 14, 2022
• Primary Completion (Estimated): November 1, 2032
• Study Completion (Estimated): November 1, 2032
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

DK (2); KR (5); TW (3); FR (10); CZ (4); ES (10); NL (5); CN (2); IL (4); JP (3); DE (6); US (18); HU (4)