Evaluation of Tafasitamab in Pediatric Patients with Relapsed or Refractory Acute B Lineage Leukemia: A Phase I/II, Single-Arm, Open-Label, Multicenter Study

The primary objective of this study is to evaluate the time until **hematological relapse** (defined as > 5% leukemic blasts) or an increase of minimal residual disease (MRD) by ≥ 2 log in bone marrow over an observation period of 545 days, accounting for competing risks. This is clinically relevant as it provides insight into the efficacy of **tafasitamab** in delaying disease progression in pediatric patients with relapsed or refractory acute B lineage leukemia.

Secondary objectives include:

• Determining the rate of patients achieving "Success of treatment," defined as survival without newly emerging MRD or increasing MRD by ≥ 2 log in bone marrow or peripheral blood, or experiencing unacceptable toxicity/infections.
• Evaluating overall survival.
• Assessing changes in MRD during and after treatment in bone marrow aspirates, with a focus on the rate of patients achieving an MRD reduction of at least 1 log compared to baseline.
• Evaluating changes in peripheral B cell numbers by flow cytometry in peripheral blood until the end of follow-up.
• Assessing the cytotoxicity of patient-derived peripheral blood mononuclear cells (PBMCs) against cell lines (NALM) and cryopreserved autologous blasts.
• Evaluating the pharmacokinetics by measuring plasma concentrations of MOR00208 at various time points during infusion cycles.

The clinical trial involves a study population of **children** aged between 3 and 18 years, diagnosed with **leukemia in childhood**, specifically B-lineage (CD19 positive) acute lymphoblastic leukemia (ALL), including B, pro-B, pre-B, or c-ALL subtypes. The trial includes both male and female participants who are considered a vulnerable population due to their age and health condition. Participants are those who are refractory to standard treatment or have relapsed disease. They must have undergone a first or subsequent allogeneic stem cell transplantation with specific criteria regarding minimal residual disease (MRD). The sponsor has not provided the total number of participants involved in the trial. Informed consent is required from patients or their legal representatives. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is a **Phase I/II**, single-arm, open-label, multicentre study designed to evaluate the safety and efficacy of **tafasitamab** in pediatric patients with relapsed or refractory acute B lineage leukemia. The primary objective is to assess the time until hematological relapse, defined as more than 5% leukemic blasts or an increase of minimal residual disease (MRD) by at least 2 log in bone marrow, over an observation period of 545 days. The trial is expected to run from October 2022 to October 2027, with participant involvement lasting up to 545 days, depending on individual response and progression.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (3 to <18 years), B-lineage (CD19 positive) acute lymphoblastic leukemia (ALL), and refractory or relapsed disease status. Informed consent must be obtained from patients or their legal representatives. Following the screening, participants will receive the investigational product, **MINJUVI 200 mg powder for concentrate for solution for infusion**, administered via **intravenous use**. The study will include regular follow-up visits to monitor safety, efficacy, and pharmacokinetics, as well as to assess secondary endpoints such as overall survival, MRD reduction, and cytotoxicity of patient-derived peripheral blood mononuclear cells (PBMCs).

The end-of-study visit will occur at the conclusion of the observation period or upon early termination due to reasons such as unacceptable toxicity, disease progression, or withdrawal of consent. Participants may be withdrawn from the study if they experience significant adverse events or if the investigator deems it necessary for their safety. The trial will collect data on primary and secondary endpoints, including treatment success rates, safety profiles, and adverse events, which will be presented in cumulative tabulations and line listings.

The clinical trial involves the administration of **MINJUVI**, a pharmaceutical product containing the active substance **tafasitamab**. **MINJUVI** is formulated as a **powder for concentrate for solution for infusion** and is intended for **intravenous use**. The product is supplied in a dosage of **200 mg** per vial. The administration schedule and frequency are determined by the study protocol, which is designed to evaluate the safety and efficacy of **tafasitamab** in pediatric patients with relapsed or refractory acute B lineage leukemia. The active substance, **tafasitamab**, is a humanized Fc-engineered monoclonal antibody targeting CD19, classified under the ATC code **L01FX12**. The product is manufactured by **INCYTE BIOSCIENCES DISTRIBUTION B.V.** and is not a pediatric formulation.

In this study, **MINJUVI** is the sole experimental treatment, and no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is a single-arm, open-label study, meaning all participants receive the experimental medication without a control group for comparison. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The primary objective is to assess the time until hematological relapse or an increase in minimal residual disease (MRD) in the bone marrow over an observation period of 545 days.

The efficacy of the clinical trial evaluating **Tafasitamab** in pediatric patients with relapsed or refractory acute B lineage leukemia will be assessed using several primary and secondary endpoints. The primary endpoint is the time until hematological relapse, defined as more than 5% leukemic blasts, or an increase of minimal residual disease (MRD) by at least 2 log in the bone marrow, observed over a period of 545 days while accounting for competing risks.

Secondary endpoints include the rate of patients achieving treatment success, characterized by survival without newly emerging MRD or an increase of MRD by at least 2 log in bone marrow or peripheral blood, or experiencing unacceptable toxicity. Additional secondary endpoints are overall survival, the rate of patients with an MRD reduction of at least 1 log at any time point compared to baseline MRD measurement between stem cell transplantation (SCT) and the start of study treatment, and B cell numbers. The cytotoxicity of patient-derived peripheral blood mononuclear cells (PBMCs) against cell lines and cryopreserved autologous blasts will also be evaluated at several time points. Pharmacokinetics of **MOR00208** will be assessed, alongside safety endpoints such as any toxicity irrespective of grade, number of deaths, number of relapses, and adverse events, which will be presented in line listings and cumulative tabulations.