Phase 2 Study on Epcoritamab Monotherapy or Combined with Lenalidomide for Anthracycline-Ineligible Diffuse Large B-Cell Lymphoma Patients

The primary objective of this study is to evaluate the **clinical efficacy** of **epcoritamab** monotherapy or in combination with **lenalidomide** as a first-line treatment for patients with **Diffuse Large B-Cell Lymphoma** who are ineligible for anthracycline-based therapies. This evaluation is clinically relevant as it aims to provide alternative therapeutic options for a patient population with limited treatment choices, potentially improving outcomes and quality of life.

Secondary objectives include: - Evaluating other efficacy measures of epcoritamab monotherapy or in combination with lenalidomide. - Assessing the **safety** and **tolerability** of these treatment regimens. - Evaluating the **immunogenicity** of epcoritamab. - Assessing the **pharmacokinetics** of epcoritamab. - Evaluating patient-reported outcomes related to lymphoma symptoms.

The clinical trial involves a total of **38 participants** diagnosed with **diffuse large B-cell lymphoma**. The study population includes both male and female subjects, with an age range of 18 years and older. Participants were selected based on specific inclusion criteria, such as having newly diagnosed CD20+ large cell lymphoma and being ineligible for anthracycline-based therapy due to age or comorbid conditions. The trial excludes vulnerable populations. Participants are required to have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2, although an ECOG PS of 3 may be considered if impairment is attributed to the current lymphoma and improves with pre-phase treatment. The study does not specify any particular lifestyle considerations such as diet or physical activity. All participants must have measurable disease as per Lugano criteria and acceptable organ function based on baseline bloodwork. Fresh or archival biopsy material is required at screening.

The clinical trial is designed as a **randomized**, open-label, multicenter, global Phase 2 study to evaluate the efficacy and safety of **epcoritamab** as monotherapy or in combination with **lenalidomide** for patients with **diffuse large B-cell lymphoma** who are ineligible for anthracycline-based therapy. The trial aims to assess the clinical efficacy of the treatments, with the primary endpoint being the complete response rate determined by the Lugano criteria. Secondary endpoints include duration of response, progression-free survival, and overall survival, among others.

The trial is expected to last until August 2027, with recruitment having started in November 2022. Participants will be involved in the study for a maximum treatment period of 12 months. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, comorbid conditions, and disease stage; regular follow-up visits to monitor treatment response and safety; and an end-of-study visit to assess final outcomes and gather data on long-term effects.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The trial will utilize a combination of oral and subcutaneous administration routes for the investigational products, with **epcoritamab** being administered subcutaneously. The study is not classified as low intervention, and it is crucial to adhere to the protocol to ensure the integrity and validity of the trial results.

The clinical trial involves the administration of several experimental and non-experimental treatments. **Epcoritamab** is a biological agent used as a test treatment in this study. It is administered as a **solution for injection** via the **subcutaneous** route. The maximum daily dose is 48 mg, and the treatment period extends up to 12 months. Epcoritamab is an anti-CD3E x anti-MS4A1 IgG1 monoclonal antibody, also known by its sponsor product code GEN3013. It is designated as an orphan drug for this trial.

**Lenalidomide** is another test treatment used in combination with Epcoritamab. It is administered **orally** with a maximum daily dose of 20 mg. The treatment period is also up to 12 months. Lenalidomide is classified under the ATC code L04AX04 and is not a pediatric formulation.

**Tocilizumab** is an auxiliary treatment in this trial, administered **intravenously**. The maximum daily dose is 800 mg, with a treatment period of up to 12 months. Tocilizumab is a protein-based biological agent, known by synonyms such as RO4877533 and BIIB800.

**Siltuximab** is another auxiliary treatment, administered **intravenously** with a dosing unit of mg/kg. The maximum daily dose is 11 mg/kg, and the treatment period is up to 12 months. Siltuximab is a chimeric anti-interleukin-6 monoclonal antibody.

**Paracetamol**, combined with buclizine hydrochloride and codeine phosphate, is administered **orally** as an auxiliary treatment. The maximum daily dose is 1000 mg, with a treatment period of up to 12 months. This combination is classified under the ATC code N02BE01.

**Anakinra** is administered **subcutaneously** as an auxiliary treatment. The maximum daily dose is 400 mg, with a treatment period of up to 12 months. Anakinra is a protein-based biological/biotechnological agent.

**Diphenhydramine** is administered **intravenously** as an auxiliary treatment. The maximum daily dose is 50 mg, with a treatment period of up to 12 months. It is classified under the ATC code R06AA02.

**Dexamethasone acetate** is administered **intravenously** as an auxiliary treatment. The maximum daily dose is 15 mg, with a treatment period of up to 12 months. It is classified under the ATC code H02AB02.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to evaluate the clinical efficacy of Epcoritamab as monotherapy or in combination with Lenalidomide for patients with diffuse large B-cell lymphoma who are ineligible for anthracycline treatment.

The clinical trial aims to evaluate the efficacy of **epcoritamab** as monotherapy or in combination with **lenalidomide** for patients with Diffuse Large B-Cell Lymphoma who are ineligible for anthracycline-based therapy. Efficacy will be primarily assessed through the complete response (CR) rate, determined by the Lugano criteria. Secondary efficacy endpoints include the duration of response (DOR), duration of complete response (DOCR), time to response (TTR), overall response rate (ORR), progression-free survival (PFS), time to next therapy (TTNT), rate and duration of minimal residual disease (MRD) negative status, and overall survival (OS). Additional assessments will include the incidence of dose-limiting toxicities (DLTs), adverse events (AEs), changes in laboratory values, incidence of antidrug antibodies (ADAs) to epcoritamab, pharmacokinetic parameters, and changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym).

The efficacy parameters will be measured and collected at various timepoints throughout the trial, with specific methods such as the Lugano criteria and FACT-Lym scale being employed. The trial is designed to ensure comprehensive data collection and analysis to determine the therapeutic impact of the investigational treatments. The trial is expected to conclude by August 2027, with recruitment having started in November 2022.