Phase 3 Multicenter Randomized Study of Epcoritamab and Lenalidomide vs. Rituximab, Gemcitabine, and Oxaliplatin in Relapsed/Refractory DLBCL

The primary objective of this study is to evaluate whether the combination of **epcoritamab** plus **lenalidomide** (E-Len) can improve outcomes as measured by progression-free survival (PFS) compared to rituximab plus gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). This is clinically relevant as improving PFS can potentially lead to better management of R/R DLBCL, a condition with limited treatment options and poor prognosis.

Secondary objectives include evaluating whether E-Len can improve outcomes as measured by the following compared to R-GemOx in R/R DLBCL:

• Complete Response Rate (CRR) determined by Lugano 2014 criteria, as assessed by an independent review committee (IRC)
• Overall survival (OS)
• Minimal residual disease (MRD) negativity rate

The clinical trial involves a total of **223 participants** diagnosed with **Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)**. The study population includes both male and female subjects, with an age range primarily encompassing adults and older adults. Participants were selected based on specific inclusion criteria, such as having histologically confirmed CD20+ DLBCL and having undergone at least one line of systemic antineoplastic therapy. The trial does not include vulnerable populations. Participants are required to have a measurable disease and an Eastern Cooperative Oncology Group Performance status score of 0 to 2. Lifestyle factors such as diet, physical activity, or habits are not specified as part of the selection criteria. The trial aims to evaluate the efficacy of epcoritamab plus lenalidomide compared to rituximab plus gemcitabine and oxaliplatin in improving progression-free survival in this patient population.

The clinical trial is a **Phase 3**, multicenter, randomized, open-label study designed to evaluate the efficacy of **epcoritamab** plus **lenalidomide** compared to **rituximab** plus **gemcitabine** and **oxaliplatin** in participants with relapsed or refractory **Diffuse Large B-Cell Lymphoma (DLBCL)**. The primary objective is to assess progression-free survival (PFS) as the main endpoint, with secondary endpoints including the percentage of participants achieving complete response (CR), overall survival (OS), and minimal residual disease (MRD) negativity rate. The trial is expected to commence recruitment on August 16, 2024, and conclude by January 17, 2028.

Participants will be randomly assigned to receive either the test regimen of epcoritamab plus lenalidomide or the comparator regimen of rituximab plus gemcitabine and oxaliplatin. The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed CD20+ DLBCL and previous treatment history. Follow-up visits will be scheduled to monitor treatment response and safety, with the end-of-study visit marking the completion of the trial for each participant.

The expected duration of participant involvement is up to 12 months, depending on the treatment arm and individual response. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The trial design ensures rigorous assessment of the investigational regimen's potential to improve outcomes in this patient population, with all procedures conducted in accordance with ethical standards and regulatory requirements.

The clinical trial involves the administration of several experimental and comparator medications. **Lenalidomide**, marketed as Revlimid, is provided in hard capsule form with dosages of 5 mg, 20 mg, and 25 mg. The capsules are administered orally. The maximum daily dose is 25 mg, with a total maximum dose of 6300 mg over a treatment period of up to 12 months. Lenalidomide is a chemical substance and is not formulated for pediatric use.

**Epcoritamab**, known by the sponsor product code GEN3013, is a bispecific antibody provided as a solution for injection. It is administered via subcutaneous injection. The dosing schedule and maximum dose amounts are not specified in the data provided. Epcoritamab is classified as a protein of other origin and is designated as an orphan drug.

**Gemcitabine** is available as a 38 mg/ml concentrate for solution for infusion. It is administered through intravenous infusion. The maximum daily dose is 1000 mg/m², with a total maximum dose of 8000 mg/m² over a treatment period of up to 4 months. Gemcitabine is a chemical substance and is not intended for pediatric use.

**Rituximab**, marketed as Truxima, is provided in two concentrations: 500 mg and 100 mg, both as concentrates for solution for infusion. It is 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 4 months. Rituximab is a protein of other origin and is not formulated for pediatric use.

**Oxaliplatin** is available as a 5 mg/ml concentrate for solution for infusion. It is administered through intravenous infusion. The maximum daily dose is 100 mg/m², with a total maximum dose of 800 mg/m² over a treatment period of up to 4 months. Oxaliplatin is a chemical substance and is not intended for pediatric use.

The efficacy of the clinical trial will be assessed using several key endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, which measures the length of time during and after the treatment that a participant lives with the disease without it getting worse. Secondary endpoints include the percentage of participants who achieve a Complete Response (CR), Overall Survival (OS), and the percentage of participants who achieve Minimal Residual Disease (MRD) negativity rate. These endpoints will provide a comprehensive evaluation of the treatment's effectiveness in participants with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL).

The trial will compare the efficacy of epcoritamab plus lenalidomide (E-Len) against rituximab plus gemcitabine and oxaliplatin (R-GemOx). The assessment of these endpoints will be conducted at various time points throughout the study, with specific intervals for data collection and analysis. The study is designed to ensure that the data collected is robust and reliable, providing a clear understanding of the treatment's impact on the disease progression and overall survival of the participants.