Epacadostat Plus Pembrolizumab and Chemotherapy for Advanced Solid Tumors: Results from the Phase I/II ECHO-207/KEYNOTE-723 Study.

ABSTRACT:

Background

Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

Methods

Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab 200 mg was infused in

SUBMITTER: Powderly JD 

PROVIDER: S-EPMC9632315 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature