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

Summary

Patients with histologically or cytologically confirmed advanced melanoma, renal cell carcinoma, NSCLC, HCC (Child Pugh Class A only), MSI-High solid tumors, Urothelial Cancer, GE junction/Gastric Adenocarcinoma, or HNSCC for which current standard of care treatment for their stage of disease would be with Pembrolizumab or Nivolumab monotherapy, who meet eligibility criteria will undergo a biopsy (core or excisional/incisional; FNA not adequate) for baseline tissue. Patients will then be randomized to one of 3 arms: Anti-PD-1 mAb plus Metformin 500mg po BID, Anti-PD-1 mAb alone, Anti-PD-1 mAb plus Rosiglitazone 4mg po qdaily. Five weeks (+/- 7 days) after initiation of therapy a patient will undergo a repeat biopsy (core or excisional/incisional; FNA not adequate) for correlative analysis. The patient will then continue on study therapy for up to 2 years, or until progression of disease or unacceptable toxicity, whichever occurs first. RECIST 1.1 with modifications, to allow for continued therapy until progressive disease is confirmed if the patient is clinically stable, will be used in the trial.

Timeline

Start

2020-09-14

Primary completion

2032-04-30

Completion

2032-04-30

Publications

• Giannitti G, Paganoni AJJ, Marchesi S, Garavaglia R, Fontana F. Mitochondrial bioenergetics and networks in melanoma: an update. Apoptosis. 2025 Oct;30(9-10):2042-2056. doi: 10.1007/s10495-025-02155-4. Epub 2025 Jul 28.
• Zandberg DP, Menk AV, Velez M, Normolle D, DePeaux K, Liu A, Ferris RL, Delgoffe GM. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck. J Immunother Cancer. 2021 May;9(5):e002088. doi: 10.1136/jitc-2020-002088.

Drugs

Indications