Phase II Study of Anti-PD-1 Therapy Alone or With Metformin or Rosiglitazone to Improve Immune Response in Advanced Solid Tumors

What this Trial Is About

This trial investigates advanced solid tumors including melanoma, renal cell carcinoma, NSCLC, hepatocellular carcinoma Child Pugh Class A, MSI-High tumors, urothelial cancer, gastric adenocarcinoma, and head and neck squamous cell carcinoma. It evaluates whether combining anti-PD-1 monoclonal antibodies with metabolic modulators Metformin or Rosiglitazone can improve immune response by reducing tumor hypoxia, compared to anti-PD-1 therapy alone. The study also assesses safety and tolerability of these combinations in a Phase II setting. Participants are randomized into three groups anti-PD-1 antibody with Metformin 500 mg twice daily, anti-PD-1 antibody with Rosiglitazone 4 mg once daily, or anti-PD-1 antibody alone. The anti-PD-1 drugs used are either nivolumab 480 mg intravenously every 4 weeks or pembrolizumab 200 mg intravenously every 3 weeks, chosen based on approved indication. Pre-treatment and post-treatment tumor biopsies are performed around 5 weeks after therapy starts. Treatment continues for up to 2 years or until disease progression or unacceptable side effects occur. During the study, participants undergo baseline and repeat tumor biopsies for analysis. They are monitored regularly for treatment response using RECIST 1.1 criteria, and safety assessments are conducted to identify adverse events. Researchers measure best overall response, progression-free survival, and overall survival up to 48 months. Participants are also evaluated for side effects attributed to the treatment throughout the study duration.

Anti-PD-1 mAb Plus Metabolic Modulator in Solid Tumor Malignancies