Phase 1/2 Evaluation of Relatlimab and Nivolumab in Pediatric and Young Adult Patients with Recurrent or Refractory Classical Hodgkin and Non-Hodgkin Lymphoma

The primary objective of this study is to characterize the **safety**, tolerability, and define the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) for the combination of **relatlimab** and **nivolumab** in pediatric participants under 18 years of age with recurrent or refractory classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL). Additionally, the study aims to characterize the pharmacokinetics (PK) of relatlimab in this population. The clinical relevance of these objectives lies in establishing a safe and effective dosing regimen for this combination therapy, which could potentially improve treatment outcomes for young patients with these challenging lymphomas.

The secondary objectives include: - Part B: To assess the safety of relatlimab and nivolumab in participants with recurrent or refractory cHL (Cohort 1) and NHL (Cohort 2). - Part B: To evaluate the overall response rate (ORR) of relatlimab and nivolumab in participants aged 30 years or younger with cHL (Cohort 1).

The clinical trial involves a total of **64 participants** diagnosed with **Recurrent or Refractory Classical Hodgkin Lymphoma** and **Non-Hodgkin Lymphoma**. The study population includes both male and female participants, with Part A focusing on individuals less than 18 years of age, and Part B including those up to 30 years old. Participants were selected based on their disease state being refractory or recurrent to standard therapy, with a requirement for measurable PET positive disease. The trial includes a vulnerable population, as it involves pediatric participants. The selection criteria ensure that participants have pathologically confirmed high-risk conditions after non-response to or failure of one or more lines of standard therapy. The study does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is designed to evaluate the **safety**, tolerability, pharmacokinetics, and preliminary efficacy of the combination of **relatlimab** and **nivolumab** in pediatric and young adult participants with recurrent or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. This is a Phase 1/2 trial, structured as a randomized, double-blind, controlled study. The trial is expected to commence recruitment on July 28, 2023, and is estimated to conclude by July 5, 2028. Participants will be involved in the study for varying durations depending on their response and tolerance to the treatment.

The study visits are sequenced to ensure comprehensive monitoring and data collection. Initially, an inclusion (screening) visit will be conducted to confirm eligibility based on the principal inclusion criteria, which include age and disease-specific requirements. Participants must have measurable PET-positive disease and a history of non-response or failure to standard therapies. Following the screening, participants will undergo regular follow-up visits to assess dose-limiting toxicities, maximum tolerated dose, and recommended phase 2 dose, as well as to monitor adverse events, serious adverse events, and laboratory abnormalities. The end-of-study visit will evaluate the complete metabolic response rate and overall response rate.

Participant involvement is expected to last until the end of the study unless early termination is warranted. Conditions that may lead to early termination include the occurrence of severe adverse events, lack of efficacy, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the therapeutic potential of the drug combination in a challenging patient population, with a focus on optimizing dosing regimens and understanding the pharmacokinetic profile of the investigational products.

The clinical trial involves the administration of two experimental medications: **Nivolumab** and **Relatlimab**. **Nivolumab**, marketed under the name OPDIVO, is provided as a 10 mg/mL concentrate for solution for infusion. It is a biological product of biotechnological origin, specifically a protein, and is administered via **intravenous use**. The pharmaceutical form is a solution for infusion, and the administration schedule is determined based on the study protocol, which aims to evaluate its safety, tolerability, and pharmacokinetics in pediatric and young adult participants with recurrent or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.

**Relatlimab** is also a biological product of biotechnological origin, classified as a protein. It is provided as a solution for injection and is administered via **intravenous use**. The administration of Relatlimab is conducted in combination with Nivolumab to assess the preliminary efficacy of the combination therapy. The dosing schedule and frequency are defined in the study protocol, with the objective of determining the maximum tolerated dose or recommended phase 2 dose in the target population.

Both medications are produced by Bristol-Myers Squibb, with Nivolumab being authorized under the marketing authorization number EU/1/15/1014/002 and Relatlimab under the sponsor product code BMS-986016. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol and to accurately assess the safety and efficacy outcomes.

The efficacy of the combination therapy of **relatlimab** and **nivolumab** in pediatric and young adult participants with recurrent or refractory classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) will be assessed in this clinical trial. The primary efficacy endpoint for Part B of the study is the Complete Metabolic Response (CMR) rate. This endpoint will be evaluated to determine the preliminary efficacy of the treatment regimen based on the Recommended Phase 2 Dose (RP2D) established in Part A of the trial.

Secondary efficacy endpoints include the Overall Response Rate (ORR) in Part B. The assessment of these endpoints will involve the collection and analysis of data related to the participants' response to the treatment. The trial will also monitor incidences of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and laboratory abnormalities as part of the safety and tolerability evaluation. The trial is designed to provide insights into the potential benefits of the combination therapy in the specified patient population.