A Phase II Trial of Anti-PD-1 mAb Alone or With Metformin or Rosiglitazone to Reverse Tumor Hypoxia and Immune Dysfunction in Solid Tumors

What this Trial Is About

This research aims to evaluate whether adding metabolic modulators Metformin or Rosiglitazone to anti-PD-1 monoclonal antibody (mAb) therapy can improve treatment response in patients with advanced solid tumors such as melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), MSI-High tumors, urothelial cancer, gastric adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC). The study is a Phase II clinical trial investigating if these metabolic drugs can reduce tumor hypoxia and restore immune function to work synergistically with anti-PD-1 therapy. It also assesses the safety and tolerability of these combinations. Participants are randomly assigned to one of three groups: anti-PD-1 mAb (nivolumab or pembrolizumab) alone, anti-PD-1 mAb plus Metformin 500 mg taken orally twice daily, or anti-PD-1 mAb plus Rosiglitazone 4 mg taken orally once daily. Before treatment, patients undergo a biopsy and then a second biopsy approximately five weeks after starting therapy. Treatment continues for up to two years or until disease progression or unacceptable side effects occur. Throughout the study, patients receive regular evaluations including tumor assessments using modified RECIST 1.1 criteria to monitor response and progression. Researchers track best overall response, progression-free survival, overall survival, and any treatment-related adverse events for up to 48 months. The study involves biopsies, imaging, laboratory tests, and clinical monitoring to understand the effects of the therapies on tumor and immune environment, ensuring careful safety oversight and long-term follow-up.

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