Assessment of [18F]F-AraG Uptake Changes Post-Radiotherapy in Non-Small Cell Lung Cancer, Melanoma, Breast, and Esophageal Cancers Using Nelarabine

The primary objective of this study is to assess the relative change in uptake of **[18F]F-AraG** in tumor lesions upon radiotherapy in patients with **non-small cell lung cancer**. This evaluation is clinically relevant as it may provide insights into the metabolic activity of the tumor post-radiotherapy, potentially aiding in the assessment of treatment efficacy and guiding future therapeutic decisions.

The clinical trial involves participants diagnosed with **melanoma**, breast cancer, non-small cell lung cancer, or esophageal cancer. The study population includes both male and female subjects, aged 18 years and older, who are currently undergoing immunotherapy with an anti-PD-(L)1 agent and are scheduled to receive high-dose radiotherapy. Participants are required to have a performance status of 0-2 on the ECOG Performance Scale, indicating they are in relatively good health despite their cancer diagnosis. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants. Selection criteria ensure that participants are willing and able to provide informed consent, aligning with ethical standards for clinical research. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the relative change in uptake of **[18F]F-AraG** in tumor lesions following radiotherapy in patients with **non-small cell lung cancer** (NSCLC), melanoma, esophageal cancer, or breast cancer. This is a phase II, randomized, double-blind, controlled study, with an estimated duration extending until January 2027. The trial will commence recruitment in September 2024. Participants will be administered **nelarabine** via intravenous injection, and the study will assess the efficacy of this investigational PET imaging tracer over time.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed cancer type, ongoing immunotherapy with an anti-PD-(L)1 agent, and a performance status of 0-2 on the ECOG Performance Scale. The trial will include follow-up visits to monitor changes in tracer uptake at baseline, and at 1 and 3 weeks post-radiotherapy. The primary endpoint is to assess the change in uptake of **[18F]F-AraG** in tumor lesions, with secondary endpoints focusing on defining tracer uptake in tumor lesions and lymphoid organs using optimized uptake parameters.

The expected length of participant involvement will vary, but it is anticipated to last until the end of the study in 2027, unless early termination is warranted. Conditions for early termination include withdrawal of consent, adverse events, or any other medical reasons deemed necessary by the investigator. Participants must be above 18 years of age and willing to provide written informed consent to be eligible for the study. The trial aims to provide valuable insights into the efficacy of **[18F]F-AraG** as a PET imaging tracer in the context of radiotherapy for various cancer types.

The clinical trial involves the use of **NELARABINE**, a chemical compound known as arabinofuranosylguanine (AraG), which is utilized as a **solution for injection**. The pharmaceutical form of NELARABINE is specifically designed for **intravenous administration**. This experimental medication is employed to assess the relative change in uptake of [18F]F-AraG in tumor lesions upon radiotherapy in patients with non-small cell lung cancer. The trial does not specify a pediatric formulation for NELARABINE, and it is not classified as an orphan drug. The product has been modified into a radiopharmaceutical tracer for the purposes of this study.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are explicitly mentioned. The focus is solely on the administration of NELARABINE to evaluate its efficacy in imaging studies related to radiotherapy. The trial documentation does not provide specific details regarding the dosing schedules or the monitoring of participant compliance. The study aims to provide insights into the changes in [18F]F-AraG uptake following radiotherapy, contributing to the understanding of treatment effects in non-small cell lung cancer.

Efficacy in this clinical trial will be assessed by evaluating the relative change in uptake of **[18F]F-AraG** in tumor lesions following radiotherapy in patients with non-small cell lung cancer (NSCLC). The primary endpoint involves defining tracer uptake in all tumor lesions and lymphoid organs, such as lymph nodes and spleen, using the optimized simplified uptake parameter, which includes standardized uptake value (SUV), tumor-to-blood ratio (TBR), and tumor-to-pleura ratio (TPR). Changes in uptake will be measured at baseline and then reassessed at 1 and 3 weeks post-radiotherapy. These assessments will be conducted using **[18F]F-AraG** PET scans, which are integral to the evaluation process. The trial aims to provide insights into the efficacy of the radiopharmaceutical tracer in monitoring treatment response in NSCLC patients undergoing radiotherapy.