Association Between Galectin-3 Levels and Outcomes in Patients With Renal Cell Carcinoma, Transitional Cell Carcinoma , Non Small Cell Lung Cancer, and Hepatocellular Carcinoma, Treated With PD-1/PDL-1 Inhibitors

1. Background and Rationale:: Galectin-3 (Gal-3) is a β-galactoside-binding protein involved in various biological processes, including cell proliferation, apoptosis, adhesion, and immune regulation. In cancer, Gal-3 promotes tumor progression by enhancing cell survival, metastasis, and angiogenesis. Additionally, Gal-3 can upregulate Programmed Death-Ligand 1 (PDL-1) expression on cancer cells, contributing to immune evasion. PDL-1, an immune checkpoint protein, binds to its receptor PD-1 on T cells, inhibiting their activity and allowing cancer cells to escape immune detection. The interaction between Gal-3 and PDL-1 creates an immunosuppressive tumor microenvironment, reducing the efficacy of PDL-1 inhibitor therapies. Gal-3 drives the inflammatory response and can worsen the inflammation based side effects of PD-1/PDL-1 inhibitos. Understanding this interplay is crucial for optimizing treatments and improving patient outcomes in cancer immunotherapy. The present study employs the FDA-approved, automated Architect system, initially used in cardiology, to ensure high accuracy and consistency in Gal-3 measurement. This method represents a significant advance over traditional manual ELISA kits, aiming to standardize and reproduce results across the patient cohort and to optimize the application of XGAL-3 apheresis based on robust data. The study results can help optimize the use of the XGAL-3 therapeutic apheresis as an adjuvant treatment to enhance the efficacy and reduce the side effects associated with PDL-1 inhibitors. Therefore, the aim of this study is to conduct an observational clinical trial assessing the correlation between Galectin-3 Level and immunotherapy Outcomes in renal cell carcinoma, non small cell lung cancer, and hepatocellular carcinoma patients treated with PD-1/ PDL-1 Inhibitors
2. Study Objectives:

• Primary objectives: To correlate Gal-3 levels with patient outcomes, including response to treatment, duration of response, survival, and side effects observed.
• Secondary objectives: To monitor and analyze serum Gal-3 level \& fluctuations over the course of PD-1/PDL-1 inhibitors in oncological patients.

1. Study enrollment and withdrawal: Inclusion/Exclusion Criteria:

Inclusion Criteria:

1. Must be able to read and understand the informed consent form (ICF) and follow protocol requirements
2. Patients aged>=18 years
3. Patients with renal cell carcinoma, Transitional cell carcinoma, non small cell lung cancer, and hepatocellular carcinoma
4. Patients treated with PD-1/PDL-1 inhibitors
5. Patients prior to first cycle of PD-1/PDL-1 inhibitors
6. Subjects willing to continue and take part in the study for the throughout the study duration.

Exclusion Criteria :

1. Female subject who is pregnant, lactating, or who want to get pregnant during the study period. Male subjects who want their partner to get pregnant.
2. Female of child-bearing potential who can't agree to utilize medically acceptable and reliable means of birth control during the study and for 1 month following the last dose of the study.
3. Study Design and Methodology: Study population: Oncology patients with renal cell carcinoma, non small cell lung cancer, and hepatocellular carcinoma, receiving PD-1/PDL-1 inhibitors Study duration: 3 years Number of patients: 300 patients Study type: This is a prospective, observational. study evaluating the correlation between serum Gal-3 level \& fluctuations and treatment outcome of immunotherapy based PD-1/PDL-1 inhibitors in patients with renal cell carcinoma, non small cell lung cancer, and hepatocellular carcinoma General Study design: The study will enroll participants from the Tel Aviv Sourasky medical center who are diagnosed with renal cell carcinoma, non small cell lung cancer, and hepatocellular carcinoma, and treated with PD-1/PDL-1 based immunotherapy Methodology
4. Data Collection: clinical and laboratory data will be collected before treatment, including blood count and chemistry included liver function In addition, disease characteristics , demographic data (age, sex), treatment-related information (concomitant medications, dosages), and documentation of adverse events will be recorded each evaluation. All data will be entered into the CRF in accordance with study procedures.
5. Gal-3 blood levels: collected of 3 ml before every immunotherapy administration per treatment
6. Gal-3 blood levels testing method

• Gal-3 blood level withdrawn of 3 ml each visit before each treatment
• Samples will be frozen at -80°C microbiology lab and analyzed in pre-determined group size or periodical testing.
• Utilize the ARCHITECT platform for all testing, with reagents supplied by Eliaz Therapeutics Inc, ensuring consistency and reliability in test results.

1. Statistical analysis: Upon trial completion, the possible correlation between Gal-3 levels and immunotherapy outcomes will be analyzed.