Evaluation of Tafasitamab and Lenalidomide Efficacy and Safety in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients Ineligible for HDC/ASCT

The primary objective of this Phase 3, single-arm, open-label, multicenter study is to determine the **efficacy** of tafasitamab plus lenalidomide in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy/autologous stem cell transplant (HDC/ASCT). The evaluation is conducted using the 2014 Lugano Classification, which is clinically relevant as it provides a standardized method for assessing treatment response in lymphoma, thereby facilitating the comparison of therapeutic outcomes.

Secondary objectives include:

• Further evaluation of additional efficacy outcomes in study participants using the 2014 Lugano Classification.
• Determination of the safety and tolerability of tafasitamab plus lenalidomide in study participants.

The clinical trial involves a total of **14 participants** diagnosed with **diffuse large B-cell lymphoma (DLBCL)**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their diagnosis of DLBCL, including subtypes such as T cell/histiocyte-rich large B-cell lymphoma and Epstein-Barr virus positive DLBCL of the elderly, among others. The trial specifically targets individuals who are not eligible for high-dose chemotherapy/autologous stem cell transplant (HDC/ASCT). Participants are required to have a histologically-confirmed diagnosis and must be willing to undergo necessary tumor and bone marrow biopsies. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that additional ethical considerations are in place to protect these participants.

The clinical trial is designed to evaluate the **efficacy** and safety of a combination therapy involving **tafasitamab** and **lenalidomide** in participants with relapsed or refractory **diffuse large B-cell lymphoma** (DLBCL). This is a Phase 3, single-arm, open-label, multicenter study. The trial aims to assess the overall response rate (ORR) and duration of response (DOR) among participants who are not eligible for high-dose chemotherapy and autologous stem cell transplant (HDC/ASCT), using the 2014 Lugano Classification. The study is expected to run from July 2022 to August 2026, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, ability to consent, and histologically-confirmed diagnosis of DLBCL or related subtypes. The screening process will also involve tumor biopsy and bone marrow biopsy/aspirate collections as necessary. Following the screening, participants will receive the investigational products, **MINJUVI** (tafasitamab) administered intravenously, and **Zelvina** (lenalidomide) in oral capsule form, with dosages tailored to the study protocol.

Throughout the trial, participants will attend regular follow-up visits to monitor their response to treatment and any adverse effects. These visits will include assessments of the primary endpoint, ORR, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) as per independent review committee (IRC) assessment. Secondary endpoints, such as DOR, will also be evaluated, measuring the time from the first documented CR or PR until disease progression or death.

The expected length of participant involvement is up to 12 months, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. The trial's design ensures rigorous monitoring and data collection to support the evaluation of the investigational therapy's safety and efficacy in the target population.

The clinical trial involves the administration of **tafasitamab**, marketed under the name Minjuvi, which is provided as a 200 mg powder for concentrate for solution for infusion. This pharmaceutical form is intended for **intravenous use**. The active substance, tafasitamab, is a humanized Fc-engineered monoclonal antibody targeting CD19, classified under the ATC code L01FX12. The maximum daily dose is 12 mg/kg, with a total treatment period of up to 12 months. The product is manufactured by Incyte Biosciences Distribution B.V. and is designated as an orphan drug for this study.

In addition to tafasitamab, the study includes the administration of **lenalidomide**, available in various dosages as hard capsules under the brand name Zelvina. The dosages include 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg capsules. Lenalidomide is administered orally, with a maximum daily dose of 25 mg and a cumulative dose limit of 6300 mg over the treatment period. The pharmaceutical form is classified under the ATC code L04AX04. The manufacturer of Zelvina is Adalvo Limited. The treatment duration for lenalidomide is also set for a maximum of 12 months.

Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed regimen. The study aims to evaluate the safety and efficacy of the combination of tafasitamab and lenalidomide in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy or autologous stem cell transplant (HDC/ASCT), following the 2014 Lugano Classification criteria.

The efficacy of the combination of **tafasitamab** and lenalidomide in participants with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) will be assessed using the 2014 Lugano Classification. The primary endpoint for evaluating efficacy is the Overall Response Rate (ORR), which is defined as the percentage of participants achieving a best response of Complete Response (CR) or Partial Response (PR) as assessed by an Independent Review Committee (IRC). Secondary endpoints include the Duration of Response (DOR), which measures the time from the first documented CR or PR until the first documented disease progression or death from any cause, whichever occurs first, among participants who achieve CR or PR per IRC assessment.