Altering the gut microbiome and TME in advanced liver cancers: A phase II study of nivolumab, tadalafil, and oral vancomycin in refractory HCC or liver-dominant metastatic CRC or PDAC.
Abstract
e14642 Background: The gut-liver axis shapes the environment that promotes liver disease. In murine models of liver cancer, our group showed that altering gut microbiome with oral vancomycin can induce an antitumor effect by modifying bile acids (BA) that then recruit natural killer T cells (NKTC). However, these NKTC were met by an immunosuppressive counter-regulatory response where myeloid-derived suppressor cells (MDSC) accumulated, impairing their cytotoxicity. Tadalafil, a PDE5 inhibitor, can suppress these MDSC in the TME. The aim of this study was to examine if the immunomodulatory effects of oral vancomycin and tadalafil can enhance nivolumab activity in advanced primary liver cancer or liver metastases. Methods: This is a phase II study of adult patients (pts) with refractory hepatocellular carcinoma (HCC) or liver-dominant metastatic colorectal (mCRC) or pancreatic (mPDAC) cancers. Pts received IV nivolumab 480mg on D1, oral vancomycin 125mg every 6 hours on D1-21, and tadalafil 10mg once daily in 28d cycles until disease progression or unacceptable toxicity. Primary endpoint was best overall response (BOR) according to RECIST v1.1. Secondary endpoints included safety/tolerability and mOS. Correlative studies were performed on paired stool, blood, and tumor biopsies. Results: From 6/2019 - 7/2021, 22 heavily pretreated pts were enrolled: 6 HCC, 9 PDAC, 7 CRC. Median age was 63y (41-82), and 27% were female. Molecular testing showed MSS, TMB low to intermediate…
Read the paper
Related studies
- Protective effects of tadalafil and N-acetyl cysteine therapy on cisplatin-induced testicular toxicity
- Understanding and treating ejaculatory dysfunction in men with diabetes mellitus
- An Eco-Friendly Solid-State Electrode Modified With ZnO Nanoparticles Decorated With MWCNT as an Electrochemical Sensor for the Determination of Avanafil in Pure Form, Dosage Form and Human Plasma
- The Use of Generative AI for Scientific Literature Searches for Systematic Reviews: ChatGPT and Microsoft Bing AI Performance Evaluation
- Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability
- Return to Sport, Reinjury Rate, and Tissue Changes after Muscle Strain Injury: A Narrative Review
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.