Evaluation of Safety, Tolerability, and Anti-Tumor Activity of IMA402 in Recurrent/Refractory Solid Tumors: A Phase I/II Clinical Trial

The primary objectives of this Phase I/II clinical trial are to evaluate the **safety**, tolerability, and anti-tumor activity of IMA402, a bispecific T cell-engaging receptor molecule targeting PRAME, in patients with recurrent and/or refractory **solid tumors**. Specifically, the study aims to:

• Determine the maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) for IMA402 during Phase I.
• Characterize the safety and tolerability of IMA402 across both Phase I and Phase II.
• Evaluate the anti-tumor activity of IMA402 in Phase II.

These objectives are clinically relevant as they aim to establish a safe and effective dosing regimen for IMA402, potentially offering a new therapeutic option for patients with challenging solid tumor profiles. No secondary objectives are specified for this study.

The clinical trial involves a total of **25 participants** diagnosed with **solid tumors**. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on specific criteria, including having pathologically confirmed and documented advanced and/or metastatic solid tumors with defined PRAME tumor target expression, confirmed HLA status, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The participants are required to have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Additionally, participants must have received or not be eligible for all available indicated standard-of-care treatments and possess adequate baseline hematologic, renal, and hepatic function, along with acceptable coagulation status. The trial includes a vulnerable population, and lifestyle factors such as diet and physical activity are not specified. The selection process ensures a focus on individuals who meet these stringent health and medical criteria to evaluate the safety, tolerability, and anti-tumor activity of IMA402.

The clinical trial is designed to evaluate the safety, tolerability, and anti-tumor activity of **IMA402**, a bispecific T cell-engaging receptor molecule, in patients with recurrent and/or refractory **solid tumors**. This trial is structured as a Phase I/II study, employing a randomized, double-blind, and controlled methodology. The trial is expected to commence recruitment on August 31, 2023, and conclude by September 30, 2027. The primary objectives include determining the maximum tolerated dose and recommended doses for extensions in Phase I, as well as assessing the anti-tumor activity in Phase II.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, tumor type, HLA status, and performance status. Following successful screening, participants will be randomized to receive the investigational product, **IMA402**, via intravenous infusion. The trial will include multiple follow-up visits to monitor safety and efficacy, with assessments for dose-limiting toxicities, treatment-emergent adverse events, and objective response rates. The end-of-study visit will mark the completion of the participant's involvement, which is anticipated to last until the trial's conclusion unless early termination criteria are met.

Participants may be withdrawn from the study prematurely if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it in the participant's best interest. The trial will utilize **human serum albumin** and **tocilizumab** as auxiliary products, also administered via intravenous infusion. The study's endpoints focus on the number of patients with dose-limiting toxicities, treatment-emergent adverse events, and the objective response rate based on RECIST v1.1 criteria. The trial's design ensures rigorous monitoring and data collection to achieve its scientific objectives.

The clinical trial involves the administration of **IMA402**, a bispecific T cell receptor (TCR)-antibody fusion protein (TCER®), as the experimental medication. **IMA402** is formulated as a **solution for infusion** and is administered via **intravenous infusion**. The primary objective of the trial is to determine the maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) for **IMA402** in Phase I, and to evaluate its safety, tolerability, and anti-tumor activity in Phase II. The active substance, **IMA402**, is a protein of other origin, developed by Immatics Biotechnologies GmbH. The dosing schedule and frequency of administration are determined based on the trial phase and participant response, with compliance monitored throughout the study.

In addition to the experimental treatment, the trial utilizes **Human Serum Albumin** as an auxiliary treatment. **Human Serum Albumin** is also provided as a **solution for infusion** and administered via **intravenous infusion**. It is a structurally diverse substance derived from blood, serving as a supportive treatment to maintain physiological conditions during the trial. The administration of **Human Serum Albumin** is conducted in accordance with standard clinical practices, ensuring participant safety and treatment efficacy.

Another auxiliary treatment used in the trial is **Tocilizumab**, which is administered as a **solution for infusion** through **intravenous infusion**. **Tocilizumab** is a protein of other origin and is included in the study to manage potential inflammatory responses associated with the experimental treatment. The administration of **Tocilizumab** follows established dosing guidelines, with careful monitoring of participant compliance and response to therapy. The inclusion of these auxiliary treatments aims to enhance the overall safety and effectiveness of the clinical trial.

Efficacy in this clinical trial will be assessed through several primary endpoints. The trial aims to evaluate the **anti-tumor activity** of IMA402, a bispecific T cell-engaging receptor molecule targeting PRAME, in patients with recurrent and/or refractory solid tumors. The primary efficacy endpoint for Phase II is the objective response rate, which will be determined based on the best overall response of complete response and partial response. This will be locally assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

The trial will also monitor the number of patients experiencing dose-limiting toxicities during Phase I, as well as the number of patients with treatment-emergent adverse events (TEAEs) and serious TEAEs during both Phase I and Phase II. Additionally, the frequency and duration of dose interruptions, reductions, and permanent discontinuations will be recorded. These parameters will provide a comprehensive evaluation of the efficacy and safety profile of IMA402 in the targeted patient population.