Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer.

International Journal of Cancer. Journal International Du Cancer
M D HellmannRebecca S Heist

Abstract

Epacadostat is a potent and highly selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). Here we report results from the open-label, dose-escalation, Phase 1b ECHO-110 study evaluating epacadostat plus atezolizumab in patients with previously treated Stage IIIB/IV nonsmall cell lung cancer (NSCLC). Eligible patients had received ≥1 prior line of platinum-based chemotherapy (≥2 cycles) and no prior checkpoint/IDO inhibitors treatment. Oral epacadostat (25, 50, 75, 100, 200 or 300 mg) was administered twice daily (BID) with intravenous atezolizumab 1,200 mg every 3 weeks (Q3W). Primary endpoints were safety, tolerability and dose-limiting toxicities (DLTs). Twenty-nine patients received ≥1 dose of treatment. The maximum tolerated dose of epacadostat was not reached. Two patients had DLTs: one patient with Grade 3 dehydration and hypotension (epacadostat 200 mg BID); one patient with Grade 3 hyponatremia and Grade 4 autoimmune encephalitis (epacadostat 300 mg BID). Twenty-three patients (79%) had treatment-related adverse events (AEs); seven patients (24%) experienced Grade 3/4 events; five patients (17%) discontinued treatment due to treatment-related AEs. No fatal treatment-related AEs occurred. One patient achieved a par...Continue Reading

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Citations

Jul 10, 2020·Ocular Immunology and Inflammation·Ruby A ParikhMeghan K Berkenstock
Sep 21, 2020·Journal of Cancer Research and Clinical Oncology·Takeshi IwasakiYoshinao Oda
Sep 17, 2020·Oncoimmunology·Julie Le NaourErika Vacchelli
Sep 19, 2020·Chinese Medical Journal·Hao-Hua ZhuXing-Sheng Hu
May 1, 2021·International Journal of Molecular Sciences·Martina MandaranoMaria Laura Belladonna

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Methods Mentioned

BETA
GTPase
biopsy

Clinical Trials Mentioned

NCT02298153
NCT03322540
NCT03322566

Software Mentioned

Phoenix WinNonlin
Incyte
epacadostat

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