Phase 3 Open-Label Evaluation of Epcoritamab with Rituximab and Lenalidomide in Relapsed/Refractory Follicular Lymphoma

The primary objective of this study is to evaluate the **efficacy**, safety, and tolerability of **epcoritamab** in combination with lenalidomide and rituximab (R2) compared to R2 alone in participants with relapsed or refractory follicular lymphoma. This is clinically relevant as it aims to determine whether the addition of epcoritamab can enhance treatment outcomes for patients with this challenging condition, potentially offering a more effective therapeutic option.

The secondary objective of this study is to evaluate whether epcoritamab in combination with R2 compared to R2 alone can improve clinical outcomes as measured by key secondary endpoints, including complete response, overall survival, and minimal residual disease negativity in participants with relapsed or refractory follicular lymphoma.

The clinical trial involves a total of **263 participants** diagnosed with **relapsed and refractory follicular lymphoma**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2, and the presence of measurable lesions as confirmed by imaging techniques. The trial does not include vulnerable populations. Participants must have histologically confirmed classic follicular lymphoma, stage II, III, or IV, without evidence of transformation to an aggressive lymphoma, and must have relapsed or refractory disease to at least one prior systemic regimen containing an anti-CD20 monoclonal antibody in combination with chemotherapy. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to evaluate the efficacy, safety, and tolerability of epcoritamab in combination with lenalidomide and rituximab compared to the latter two alone.

The clinical trial is designed to evaluate the **efficacy**, safety, and tolerability of **epcoritamab** in combination with **lenalidomide** and **rituximab** (R2) compared to R2 alone in participants with relapsed or refractory follicular lymphoma. This is a Phase III, open-label study, which involves a randomized, controlled trial design. The trial is expected to run until June 17, 2030, with recruitment having commenced on September 20, 2022. Participants will be involved in the study for a maximum treatment period of 48 weeks, depending on the specific treatment arm they are assigned to.

The study visits are structured to include an initial screening visit, where eligibility is assessed based on criteria such as an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2, and the presence of measurable disease as confirmed by imaging techniques. Following the screening, participants will undergo regular follow-up visits to monitor treatment response and safety. These visits will include assessments of progression-free survival and overall response, as determined by the Lugano criteria. The end-of-study visit will conclude the participant's involvement, where final evaluations of safety and efficacy will be conducted.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The primary endpoints of the study include progression-free survival and the best overall response, while secondary endpoints focus on the percentage of participants achieving complete response, overall survival, and minimal residual disease negativity. The trial aims to provide comprehensive data on the potential benefits of adding epcoritamab to the R2 regimen in this patient population.

The clinical trial involves the administration of several treatments, including **Truxima**, **Revlimid**, and **Epcoritamab**. **Truxima** is available in two formulations: a 100 mg and a 500 mg concentrate for solution for infusion. The active substance in Truxima is **rituximab**, a protein-based therapeutic agent. The pharmaceutical form is a solution for infusion, administered via **intravenous infusion**. The maximum daily dose is 375 mg/m², with a total maximum dose of 3000 mg/m² over a treatment period of up to 20 weeks. The administration schedule and participant compliance are monitored throughout the study.

**Revlimid** is provided in two dosages: 5 mg and 20 mg hard capsules. The active substance is **lenalidomide**, a chemical compound. The pharmaceutical form is a hard capsule, administered **orally**. The maximum daily dose is 20 mg, with a total maximum dose of 5040 mg over a treatment period of up to 36 weeks. The dosing schedule is strictly adhered to, and participant compliance is closely monitored to ensure accurate data collection.

**Epcoritamab** (GEN3013) is a bispecific antibody provided as a solution for injection. The active substance is **epcoritamab**, a protein-based therapeutic agent. The pharmaceutical form is a solution for injection, administered via **subcutaneous injection**. The treatment period can extend up to 48 weeks. Although the maximum daily and total doses are not specified, the administration is carefully controlled, and participant adherence is monitored to maintain the integrity of the trial data.

In this study, the combination of **epcoritamab** with **rituximab** and **lenalidomide** (R2) is compared to R2 alone in subjects with relapsed or refractory follicular lymphoma. The trial aims to evaluate the efficacy, safety, and tolerability of these combinations. No placebo or additional comparator treatments are used in this study. The trial is conducted under strict regulatory compliance, ensuring the safety and well-being of all participants.

The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)** and the best overall response (BOR) of complete response (CR) or partial response (PR), determined by the Lugano criteria, as assessed by an Independent Review Committee (IRC). Secondary endpoints will evaluate the percentage of participants achieving complete response (CR), overall survival (OS), and the percentage of participants achieving minimal residual disease (MRD) negativity.

The trial is designed to compare the efficacy of **epcoritamab** in combination with **rituximab** and **lenalidomide** (R2) against R2 alone in subjects with relapsed or refractory follicular lymphoma. The efficacy parameters will be measured and collected at specified intervals throughout the study duration, with assessments conducted by validated scales and independent review committees to ensure accuracy and reliability. The trial is expected to conclude by June 17, 2030, with recruitment having started on September 20, 2022.