Adding Indoximod to Pembrolizumab Improved Response Rate in Advanced Melanoma

In this video, Yousef N. Zakharia, MD, of the Holden Comprehensive Cancer Center and division of hematology and medical oncology at the University of Iowa, discusses phase II results of a single-arm trial that tested checkpoint inhibition plus indoximod, an IDO-pathway inhibitor, in patients with advanced melanoma.

The trial looked at 60 patients treated with investigator’s choice of nivolumab, pembrolizumab, or ipilimumab plus indoximod. The majority of patients in the trial had stage IV disease, and nearly half had visceral metastases. All patients were treatment-naive for checkpoint inhibition.

Notably, nine patients with ocular melanoma were included-these patients are often excluded from melanoma trials; one of these patients achieved a partial response.

Zakharia, who presented the data at the 2017 American Association for Cancer Research (AACR) Annual Meeting in Washington, DC, reveals the overall response data from the trial, toxicity data, and compares the results to historical data of pembrolizumab monotherapy from KEYNOTE-006, which included similar patients.

The IDO pathway is immunosuppressive and was originally described as one of the mechanisms for maternal–fetal immune tolerance. IDO is a key immunoregulatory enzyme in the metabolism of the essential amino acid tryptophan to kynurenine. Tryptophan depletion results in the inhibition of effector T cells and kynurenine accumulation results in the expansion of immune-suppressant regulatory T cells.