Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma

Phase 3

Active, not recruiting

• Conditions: Follicular Lymphoma (FL)
• Interventions: Drug: Epcoritamab; Drug: Rituximab; Drug: Lenalidomide

• Registration Number: NCT05409066
• Lead Sponsor: Genmab

Brief Summary

Follicular Lymphoma (FL) is the second most common B-cell cancer and the most common type of cancer of lymphocytes. Unfortunately, this disease is incurable with conventional treatment and the disease recurs in almost all patients. This study will assess how safe and effective epcoritamab is in combination with lenalidomide and rituximab (R2) in treating adult participants with relapsed or refractory (R/R) FL. Adverse events and change in disease condition will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of FL. Study doctors put the participants in 1 of 3 groups, called treatment arms. Each group receives a different treatment. Enrollment to one of the groups is closed. Around 500 adult participants with R/R FL will be enrolled in approximately 300 sites across the world.

Participants will receive R2 (375 mg/m\^2 intravenous infusion of rituximab up to 5 cycles and oral capsules of 20 mg lenalidomide for up to 12 cycles) alone or in combination with subcutaneous injections of epcoritamab for up to 12 cycles (each cycle is 28 days).

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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-03
• Study First Submitted QC: 2022-06-03
• Study First Posted: 2022-06-08
• Study Start: 2022-09-20
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-23
• Last Update Posted: 2025-07-28
• Primary Completion: 2029-12
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 549

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2.

• Participant has:

  • Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrating positive lesion compatible with computed tomography (CT) or magnetic resonance image (MRI)-defined anatomical tumor sites AND
  • >= 1 measurable nodal lesion (long axis > 1.5 cm) or >= 1 measurable extra-nodal lesion (long axis > 1.0 cm) on CT scan or MRI.

• Histologically confirmed classic follicular lymphoma (FL) [previously Grade 1 to 3a FL] stage II, III, or IV with no evidence of histologic transformation to an aggressive lymphoma and CD20+ disease on most recent representative tumor biopsy based on the pathology report.

• Relapsed or refractory (R/R) disease to at least one prior systemic regimen that contained an anti-CD20 monoclonal antibody (mAb) in combination with chemotherapy. (Participant who received only prior anti-CD20 mAb monotherapy and/or radiation therapy is not eligible.)

• Eligible to receive R2 per investigator determination.

• Estimated Creatinine Clearance (CrCl) >= 50 mL/min.

Exclusion Criteria

• Documented refractoriness to lenalidomide.
• Have lenalidomide exposure within 12 months prior to randomization.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epcoritamab Dose A in Combination With R2	Epcoritamab	Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).
Epcoritamab Dose A in Combination With R2	Rituximab	Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).
Epcoritamab Dose A in Combination With R2	Lenalidomide	Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).
Epcoritamab Dose B in Combination With R2	Epcoritamab	Participants will receive epcoritamab Dose B in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). Enrollment is closed for this arm.
Epcoritamab Dose B in Combination With R2	Rituximab	Participants will receive epcoritamab Dose B in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). Enrollment is closed for this arm.
Epcoritamab Dose B in Combination With R2	Lenalidomide	Participants will receive epcoritamab Dose B in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). Enrollment is closed for this arm.
Lenalidomide and Rituximab (R2)	Rituximab	Participants will receive lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).
Lenalidomide and Rituximab (R2)	Lenalidomide	Participants will receive lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Best Overall Response (BOR)	Up to approximately 5 years	BOR is defined as Complete Response (CR) or Partial Response (PR), determined by Lugano criteria, as assessed by an IRC.
Progression-Free Survival (PFS)	Up to approximately 5 years	PFS is defined as duration from the date of randomization to the date of disease progression determined by Lugano criteria by independent review committee (IRC) or death (whichever occurs first).

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to approximately 8 years	DOR is defined as the time from the first occurrence of response (CR or PR) to disease progression or death, whichever occurs first.
Duration of Complete Response (DOCR)	Up to approximately 8 years	DOR is defined as the time from the first occurrence of CR to disease progression or death, whichever occurs first.
Time to Progression (TTP)	Up to approximately 8 years	Time to progression is defined as the number of days from the date of study drug start to the date of the first documented disease progression or relapse.
Time to Next Anti-Lymphoma Treatment (TTNLT)	Up to approximately 8 years	Time to next anti-lymphoma treatment is defined as the number of days from the date of the first documented disease progression or relapse to the date of next anti-lymphoma treatment.
Percentage of Participants Achieving CR at the End of Treatment	Up to approximately 5 years	Percentage of participants who achieve a CR determined per Lugano criteria, as assessed by the IRC prior to the initiation of subsequent anti-lymphoma therapy.
Time to Response (TTR)	Up to approximately 8 years	Time to response is defined for participants achieving a CR/PR as the time from starting therapy to first a CR/PR.
Time to Complete Response (TTCR)	Up to approximately 8 years	Time to complete response is defined for participants achieving a CR/PR as the time from starting therapy to first a CR/PR.
Event-Free Survival (EFS)	Up to approximately 8 years	EFS is defined as the duration from randomization to disease progression determined by Lugano criteria as assessed by the investigator, initiation of any non-protocol-specified new anti-lymphoma therapy for any reason, or death (whichever occurs first).
Change in Patient's Global Impression of Severity (PGIS)	Up to approximately 8 years	PGIS is a self-report measure PGIS reflects a participant's belief about their lymphoma symptoms over the past 7 days. The PGIS is a 5-point scale depicting a participant's rating of overall severity. Participants rate their lymphoma symptoms severity as none, mild, moderate, severe, or very severe.
Percentage of Participants Achieving CR	Up to approximately 5 years	Percentage of participants who achieve a CR determined per Lugano criteria, as assessed by the IRC prior to the initiation of subsequent anti-lymphoma therapy.
Overall Survival (OS)	Up to approximately 8 years from randomization	Overall survival is defined as the duration from the date of randomization to the date of the participant's death.
Percentage of Participants Achieving Minimal Residual Disease (MRD) Negativity	Up to approximately 5 years	MRD negativity rate is defined as the percentage of participants who achieve MRD negative status prior to the initiation of subsequent anti-lymphoma therapy.
Change in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)	Up to approximately 8 years	The objective of the FACT-Lym patient-reported outcome (PRO) is to address health-related quality of life issues for adult lymphoma patients. It utilizes a 5-point Like-type scale, with a higher score signifying a higher quality of life.
PFS as Assessed by Investigator	Up to approximately 5 years	PFS is defined as duration from the date of randomization to the date of disease progression determined by Lugano criteria by investigator or death (whichever occurs first).
Percentage of Participants Achieving BOR as Assessed by Investigator	Up to approximately 5 years	BOR is defined as CR PR, determined by Lugano criteria, as assessed by an investigator.
Percentage of Participants Achieving CR as Assessed by Investigator	Up to approximately 5 years	Percentage of participants who achieve a CR determined per Lugano criteria, as assessed by the investigator prior to the initiation of subsequent anti-lymphoma therapy.
Time to next anti-lymphoma treatment (TTNLT)	Up to approximately 8 years
Change in Patient's Global Impression of Change (PGIC)	Up to approximately 8 years	PGIS is a self-report measure PGIC reflects a participant's belief about the efficacy of treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement since start of treatment. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Change in EuroQol 5-Dimension Questionnaire, 5-level (EQ-5D-5L)	Up to approximately 8 years	The EQ-5D-5L descriptive system measures health status and comprises 5 health aspects including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each parameter has 5 response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. This instrument will not be administered during the Survival Follow-Up.

Trial Locations

Locations (273)

The University of Arizona Cancer Center - North Campus /ID# 228862; 🇺🇸 Tucson, Arizona, United States

University of Arkansas for Medical Sciences /ID# 227198; 🇺🇸 Little Rock, Arkansas, United States

Alta Bates Summit Medical Center for Research /ID# 229428; 🇺🇸 Berkeley, California, United States

Beverly Hills Cancer Center /ID# 231535; 🇺🇸 Beverly Hills, California, United States

Long Beach Memorial Medical Ct /ID# 228997; 🇺🇸 Long Beach, California, United States

University of Southern California /ID# 227195; 🇺🇸 Los Angeles, California, United States

Valkyrie Clinical Trials /ID# 268502; 🇺🇸 Los Angeles, California, United States

Duplicate_Emory University /ID# 227299; 🇺🇸 Atlanta, Georgia, United States

Hawaii Cancer Care - Waterfront Plaza /ID# 262448; 🇺🇸 Honolulu, Hawaii, United States

Northwestern University Feinberg School of Medicine /ID# 227248; 🇺🇸 Chicago, Illinois, United States

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