A phase II study of nivolumab plus metformin in pre-treated metastatic renal cell carcinoma patients: NivoMet TWINS-GU002 Study

Abstract

Aims:

This study evaluates the activity of nivolumab plus metformin in pre-treated metastatic renal cell carcinoma (mRCC) patients.

Materials and Methods:

The NivoMet TWINS-GU002 Study was a prospective, multicentre, single-arm, phase II trial conducted in pre-treated mRCC patients eligible for nivolumab and without diabetes mellitus. Patients received nivolumab (240 mg every two weeks) plus metformin (500 mg orally twice a day) until disease progression. The primary endpoint was the 9-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), overall response rate (ORR), and safety.

Results:

Twelve patients from two sites in Italy were enrolled from November 2020 to April 2023. The trial was terminated early due to slow accrual. The median PFS was 2.7 months, and the 9-month PFS rate was 8%. The median OS was 14.9 months. The ORR was 8%, and the disease control rate (DCR) was 25%. Adverse events (AEs) of any grade occurred in 75% of patients, with only one grade 3 AE (fatigue) not related to treatment. No grade 3 or 4 treatment-related AEs occurred.

Conclusions:

The combination of nivolumab and metformin showed marginal activity in pre-treated mRCC patients. Further investigations are needed to explore metabolic pathways as potential therapeutic targets.