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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Open-Label Study to Evaluate Safety and Efficacy of Epcoritamab in Combination With Rituximab and Lenalidomide (R2) Compared to R2 in Subjects With Relapsed or Refractory Follicular Lymphoma (EPCORE FL-1)

Conditions
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Follicular Lymphoma (FL)

Intervention / Treatment
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* Drug: Epcoritamab
* Drug: Rituximab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Documented refractoriness to lenalidomide. Have lenalidomide exposure within 12 months prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epcoritamab Dose A in Combination With R2<br>Participants will receive epcoritamab Dose A in combination with lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). | Drug: Epcoritamab<br>* Subcutaneous Injection<br>* Other names: GEN3013;Drug: Rituximab<br>* Intravenous Infusion<br>Drug: Lenalidomide<br>* Oral Capsules<br>|
| Experimental: Epcoritamab Dose B in Combination With R2<br>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. | Drug: Epcoritamab<br>* Subcutaneous Injection<br>* Other names: GEN3013;Drug: Rituximab<br>* Intravenous Infusion<br>Drug: Lenalidomide<br>* Oral Capsules<br>|
| Active Comparator: Lenalidomide and Rituximab (R2)<br>Participants will receive lenalidomide and rituximab (R2) for 12 cycles (each cycle is 28 days). | Drug: Rituximab<br>* Intravenous Infusion<br>Drug: Lenalidomide<br>* Oral Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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). | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Complete Response (CR) | 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. | Up to approximately 5 years | 
| Overall Survival (OS) | Overall survival is defined as the duration from the date of randomization to the date of the participant's death. | Up to approximately 8 years from randomization | 
| Percentage of Participants Achieving Minimal Residual Disease (MRD) Negativity | MRD negativity rate is defined as the percentage of participants who achieve MRD negative status prior to the initiation of subsequent anti-lymphoma therapy. | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Follicular Lymphoma (FL), Non-Hodgkin's lymphoma (NHL), Lymphoma, Cancer, Epcoritamab, Rituximab, Lenalidomide, EPCORE FL-1, EPCORE