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RECRUITINGPhase 2INTERVENTIONAL

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

Phase 1b/2, Open-Label Study to Evaluate Safety and Tolerability of Epcoritamab in Combination With Anti-Neoplastic Agents in Subjects With Non-Hodgkin Lymphoma

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Diagnosis of: \-- Diffuse large B-cell lymphoma (DLBCL) (de novo or histologically transformed from follicular lymphoma (FL) or nodal marginal zone lymphoma) with diagnosed by tissue sample (biopsy-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 diagnosed by tissue sample (biopsy-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 diagnosed by tissue sample (biopsy-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). Who Should NOT Join This Trial: - Prior treatment with epcoritamab or any other bispecific antibody targeting CD3 and CD20. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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). Exclusion Criteria: * 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.

Treatments Being Tested

DRUG

Epcoritamab

Subcutaneous Injection (SC)

DRUG

Lenalidomide

Oral; Capsule

DRUG

Ibrutinib

Oral; Capsule

DRUG

Rituximab

Intravenous (IV); Injection

DRUG

Cyclophosphamide

IV; Injection

DRUG

Doxorubicin Hydrochloride [HCl]

IV; Injection

DRUG

Prednisone

Oral; Tablet

DRUG

Polatuzumab Vedotin

IV; Injection

DRUG

CC-99282

Oral; Capsule

Locations (20)

The University of Arizona Cancer Center - North Campus /ID# 242219
Tucson, Arizona, United States
Yale University School of Medicine /ID# 242089
New Haven, Connecticut, United States
Christiana Care Health Service /ID# 242301
Newark, Delaware, United States
Tampa General Hospital /ID# 246748
Tampa, Florida, United States
Winship Cancer Institute of Emory University /ID# 242153
Atlanta, Georgia, United States
University of Maryland, Baltimore /ID# 242218
Baltimore, Maryland, United States
Alliance for Multispecialty Research (AMR) - Kansas City /ID# 242144
Kansas City, Missouri, United States
Northwell Health - Monter Cancer Center /ID# 245435
Lake Success, New York, United States
Icahn School of Medicine at Mount Sinai /ID# 242123
New York, New York, United States
Novant Health Presbyterian Medical Center /ID# 242148
Charlotte, North Carolina, United States
East Carolina University - Brody School of Medicine /ID# 242506
Greenville, North Carolina, United States
Novant Health Forsyth Medical Center /ID# 242198
Winston-Salem, North Carolina, United States
Thomas Jefferson University Hospital /ID# 242077
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center /ID# 242106
Philadelphia, Pennsylvania, United States
Thompson Cancer Survival Ctr /ID# 242150
Knoxville, Tennessee, United States
Joe Arrington Cancer Research /ID# 242226
Lubbock, Texas, United States
Swedish Medical Center - Seattle /ID# 242269
Seattle, Washington, United States
MultiCare Institute for Research & Innovation /ID# 242127
Tacoma, Washington, United States
Beijing Cancer Hospital /ID# 252303
Beijing, Beijing Municipality, China
Fakultni Nemocnice Brno - Jihlavska /ID# 242683
Brno, Brno-mesto, Czechia