NCT03238638

A Study of Epacadostat + Pembrolizumab in Head and Neck Cancer Patients, Who Failed Prior PD-1/PD-L1 Therapy

A Phase II Study of Epacadostat + Pembrolizumab in Head and Neck Cancer Patients, Who Failed Prior PD-1/PD-L1 Therapy

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a research study to test the combination of two drugs, pembrolizumab and epacadostat with the goal of benefiting subjects with head and neck cancers where prior or ongoing regimens with a PD-1 or PD-L1 inhibitor for the treatment of advanced head and neck cancer after platinum failure.

Detailed description

Primary Objective(s) \& Hypothesis (1) Objective: Response Rate Hypotheses: Cohort 1: In patient with prior response to anti-PD-1/PD-L1+ therapy and subsequent (acquired) resistance combined IDO1 and PD-1 inhibition will re-induce responses. Cohort 2: In patients with suboptimal benefit from prior anti-PD-1/PD-L1 therapy combined IDO1 and PD-1 inhibition will induce clinically meaningful responses. Secondary Objective(s) \& Hypothesis 1. Objective: 1-year Progression-free (PFS) and Overall (OS) survival Hypothesis: Combined PD-1 blockade with pembrolizumab + epacadostat in HNSCC patients will lead to improved 1-year survival in patients who a) progress on prior anti-PD-1/PD/L1 therapy on, and/or b) compared to patients who progress on 2nd line chemotherapy. 2. Safety Hypothesis: Combined treatment with pembrolizumab and epacadostat will be safe and tolerable in HNSCC patients. Exploratory/Translational Objectives 1. Interferon-gamma Gene Expression Profile (GEP) (Seiwert ASCO 2015, Ribas ASCO 2015) and evaluation of RR, PFS, and OS in GEP positive and GEP negative patients. 2. Determine the micro-environment that underlies resistance/suboptimal treatment 1. underlying degree of tumor inflammation 2. Baseline PD-L1 expression d) Determine underlying Interferon Gamma signature 3. Assess underlying mutational burden (Snyder 2014)) Preclinical hypothesis: IDO1 inhibition will alter the micro-environment to a be "more T-cell inflamed" and make tumors amenable to benefit from anti-PD-1 treatment (when given concurrently with IDO1 inhibition). Hence we will evaluate tumors, with prior response exhibiting acquired resistance as well as tumors with minor/suboptimal benefit from prior PD-1/PD-L1 therapy for evidence (at baseline) of suboptimal immune microenvironmental conditions.

Conditions

• Head and Neck Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Both cohorts will receive pembrolizumab at a flat dose of 200mg every 3 weeks.
DRUG	epacadostat	Both cohorts will receive epacadostat. Patients in cohort 1 will take 300mg of epacadostat by mouth twice per day. Cohort 2 will take 300mg of epacadostat every 6 weeks.

Timeline

• Start date: 2018-09-01
• Primary completion: 2020-12-01
• Completion: 2020-12-01
• First posted: 2017-08-03
• Last updated: 2018-01-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study