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

Not Applicable

Recruiting

• Conditions: Non-Hodgkin Lymphoma
• Interventions: Drug: Epcoritamab; Drug: Ibrutinib; Drug: Lenalidomide; Drug: CC-99282; Drug: Pirtobrutinib; Drug: Rituximab; Drug: Venetoclax; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride [HCl]; Drug: Prednisone; Drug: Polatuzumab Vedotin

• Registration Number: NCT05283720
• Lead Sponsor: Genmab

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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-09
• Study First Submitted QC: 2022-03-09
• Study First Posted: 2022-03-17
• Study Start: 2022-06-14
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-07
• Last Update Posted: 2025-07-10
• Primary Completion: 2032-11
• Study Completion: 2032-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 565

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 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) 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm 7: Dose Escalation	Ibrutinib	Participants with newly diagnosed treatment-naïve MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 1: Dose Escalation	Epcoritamab	Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of subcutaneous (SC) epcoritamab in combination with oral lenalidomide in 28 day cycles.
Arm 1: Dose Escalation	Lenalidomide	Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of subcutaneous (SC) epcoritamab in combination with oral lenalidomide in 28 day cycles.
Arm 2: Dose Escalation	Epcoritamab	Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 2: Dose Escalation	Lenalidomide	Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 2: Dose Escalation	Ibrutinib	Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 3: Dose Escalation	Doxorubicin Hydrochloride [HCl]	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 4: Dose Escalation	CC-99282	Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 5: Dose Escalation	CC-99282	Participants with R/R follicular lymphoma (FL) will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 5: Dose Expansion	CC-99282	Participants with R/R FL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 3: Dose Expansion	Doxorubicin Hydrochloride [HCl]	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 4: Dose Expansion	CC-99282	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 6: Dose Expansion	Epcoritamab	Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.
Arm 6: Dose Expansion	Ibrutinib	Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.
Arm 7: Dose Expansion	Epcoritamab	Participants with newly diagnosed treatment-naïve MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 7: Dose Expansion	Ibrutinib	Participants with newly diagnosed treatment-naïve MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 7: Dose Expansion	Venetoclax	Participants with newly diagnosed treatment-naïve MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 8: Dose Expansion	Epcoritamab	Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.
Arm 8: Dose Expansion	Pirtobrutinib	Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.
Arm 3: Dose Escalation	Prednisone	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Escalation	Epcoritamab	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Escalation	Cyclophosphamide	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Escalation	Rituximab	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Escalation	Polatuzumab Vedotin	Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 4: Dose Escalation	Epcoritamab	Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 5: Dose Escalation	Epcoritamab	Participants with R/R follicular lymphoma (FL) will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 6A: Dose Escalation	Ibrutinib	Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.
Arm 6A: Dose Escalation	Epcoritamab	Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.
Arm 6B: Dose Escalation	Epcoritamab	Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 6B: Dose Escalation	Ibrutinib	Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 7: Dose Escalation	Epcoritamab	Participants with newly diagnosed treatment-naïve MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 6B: Dose Escalation	Venetoclax	Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 2: Dose Expansion	Lenalidomide	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 7: Dose Escalation	Venetoclax	Participants with newly diagnosed treatment-naïve MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.
Arm 8: Dose Escalation	Epcoritamab	Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.
Arm 8: Dose Escalation	Pirtobrutinib	Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.
Arm 1: Dose Expansion	Epcoritamab	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral lenalidomide in 28 day cycles.
Arm 1: Dose Expansion	Lenalidomide	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral lenalidomide in 28 day cycles.
Arm 2: Dose Expansion	Epcoritamab	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 3: Dose Expansion	Epcoritamab	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 2: Dose Expansion	Ibrutinib	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.
Arm 3: Dose Expansion	Rituximab	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Expansion	Polatuzumab Vedotin	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 4: Dose Expansion	Epcoritamab	Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.
Arm 3: Dose Expansion	Cyclophosphamide	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 3: Dose Expansion	Prednisone	Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.
Arm 5: Dose Expansion	Epcoritamab	Participants with R/R FL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Dose-Limiting Toxicities (DLT)	Up to Approximately 5 Years	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.

Secondary Outcome Measures

Name	Time	Method
Best Overall Response (BOR) per Investigator	Up to Approximately 5 Years	BOR is defined as the percentage of participants who achieved best overall response of CR or PR by Lugano 2014 criteria as assessed by the investigator.
Duration of response (DOR) per Investigator	Up to Approximately 5 Years	DOR is defined for participants who achieved best overall response of CR or PR ('responders'), as the time in months from initial CR/PR to the earliest occurrence of radiographic progression determined by Lugano 2014 criteria as assessed by the investigator, or death from any cause.
Number of Participants with Progression-free survival (PFS)	Up to Approximately 5 Years	PFS is defined as the time in months from the first dose of study drug to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.
Percentage of Participants with Complete Response (CR)	Up to Approximately 5 Years	CR is defined as the percentage of participantswho achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.
Time-to-response (TTR)	Up to Approximately 5 Years	TTR is defined as the number of months from the date of first dose to the date of best overall response of CR or PR ('responders') determined by Lugano 2014 criteria as assessed by investigator.
Time to Next Antilymphoma Therapy (TTNT)	Up to Approximately 5 Years	Time to next antilymphoma therapy.
Rate of Minimal Residual Disease (MRD) Negativity	Up to Approximately 5 Years	MRD is defined as the percentage of participants with assessment of the minimal residual disease.
Overall Survival (OS)	Up to Approximately 5 Years	(OS) is defined as the time in months from first dose of epcoritamab to death from any cause.

Trial Locations

Locations (74)

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

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