A Study of Atezolizumab in Combination With Epacadostat in Subjects With Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Previously Treated Stage IV Urothelial Carcinoma

A Phase 1 Study of Atezolizumab in Combination With Epacadostat in Subjects With Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Previously Treated Stage IV Urothelial Carcinoma

This study evaluated the safety and tolerability of epacadostat (INCB024360) administered in combination with atezolizumab (MPDL3280A) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that were previously treated with platinum-based chemotherapy and Stage IV urothelial carcinoma who failed a platinum-based chemotherapy regimen. The study was conducted in two phases. The dose escalation phase did utilize a 3 + 3 design to identify the maximum tolerated dose (MTD) or a Pharmacologically Active Dose (PAD) of the combination. This was followed by a dose expansion phase, which was comprised of three cohorts. Expansion Cohorts 1 & 2 will further evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics at the dose identified in phase one. Expansion Cohort 3 will evaluate the change in biomarker expression following treatment with epacadostat as monotherapy followed by epacadostat and atezolizumab administered in combination.

Study Overview

• Status: Terminated
• Conditions: UC (Urothelial Cancer); NSCLC (Non-small Cell Lung Carcinoma)
• Intervention / Treatment: Drug: Epacadostat; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Pinnacle Oncology Hematology
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Harvard-Mass General Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subjects, age 18 years or older
• Histologically or cytologically confirmed NSCLC

• Stage IIIB or Stage IV NSCLC who are not candidates for multimodality treatment and have received at least 1 line of standard platinum-based therapy:

  • Prior systemic regimens must include at least 2 cycles of a platinum-based therapy and may include platinum therapy used as a radiosensitizer. Maintenance chemotherapy is allowed.
  • Tumors with driver mutations (epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive) should have had disease progression or been intolerant to the standard tyrosine-kinase inhibitor (TKI), and should include a second line TKI where such therapy is available and indicated.
  • Subjects initially treated with a platinum regimen for Stage IIIB disease who later develop metastatic disease and are re-treated with a platinum regimen are allowed.
• Histologically or cytologically confirmed urothelial carcinoma.
• Stage IV locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Presence of measurable disease per RECIST v1.1
• Availability of an adequate archival tumor specimen or willingness to undergo a pretreatment tumor biopsy.
• Subjects enrolled in Expansion Cohort 3 must be willing to have 2 on-treatment tumor biopsies.
• For males and females of child-bearing potential, willingness to use adequate birth control through 90 days after the last dose of epacadostat or atezolizumab.

Exclusion Criteria:

• Laboratory and medical history parameters not within protocol-defined range.
• Current treatment with an investigational study drug or immunological-based agent for any reason, or receipt of anticancer medication within 21 days or 5 half-lives (whichever is longer) before first dose.
• Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor.
• Prior monoclonal antibody within 4 weeks before study Day 1, or has not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Has an active or inactive autoimmune process.
• Has a history of pneumonitis or idiopathic pulmonary fibrosis, or evidence of interstitial lung disease.
• Prior radiotherapy within 2 weeks of therapy; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Untreated central nervous system (CNS) metastases or CNS metastases that have progressed after completion of radiotherapy.
• Use of systemic corticosteroids ≤ 2 weeks before Cycle 1 Day 1.
• Currently pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epacadostat 25 mg+Atezolizumab 1200 mg; Epacadostat 25 mg tablet orally twice daily (BID) starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A
Experimental: Epacadostat 50 mg+Atezolizumab 1200 mg; Epacadostat 50 mg tablet orally BID starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A
Experimental: Epacadostat 75 mg+Atezolizumab 1200 mg; Epacadostat 75 mg tablet orally BID starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A
Experimental: Epacadostat 100 mg+Atezolizumab 1200 mg; Epacadostat 100 mg tablet orally BID starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A
Experimental: Epacadostat 200 mg+Atezolizumab 1200 mg; Epacadostat 200 mg tablet orally BID starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A
Experimental: Epacadostat 300 mg+Atezolizumab 1200 mg; Epacadostat 300 mg tablet orally BID starting on Cycle 1 Day 1 in combination with atezolizumab 1200 mg administered intravenously every 3 weeks starting on Cycle 1 Day 1.	Drug: Epacadostat; Epacadostat tablets; Other Names: INCB024360; Drug: Atezolizumab; Atezolizumab intravenously; Other Names: MPDL3280A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AEs)	Continuously for duration of study participation and up to 42 days after the last dose [approximately 8 months
Incidence of dose-limiting toxicities (DLTs)	21 days following the first administration of atezolizumab and epacadostat

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR determined by radiographic disease assessments per modified RECIST v1.1	Measured every 6 weeks for duration of study participation [approximately 8 months]
Durability of response	Time from the earliest date of disease response until earliest date of disease progression based on modified RECIST v1.1	Measured every 6 weeks for duration of study participation [approximately 8 months]
Progression-free survival	Time from date of enrollment until the earliest date of disease progression per modified RECIST v1.1 or death due to any cause, whichever is earlier.	Measured every 6 weeks for duration of study participation [approximately 8 months]
Duration of disease control	Time from first dose until report of disease progression for subjects who reported stable disease or better based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Measured every 6 weeks for duration of study participation [approximately 8 months]

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: Hoffmann-La Roche; Genentech, Inc.
• Investigators: Study Director: Hiroomi Tada, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2015
• Primary Completion (Actual): November 8, 2017
• Study Completion (Actual): November 8, 2017

Study Registration Dates

• First Submitted: October 31, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimated): November 21, 2014

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; atezolizumab; epacadostat
• Other Study ID Numbers: INCB 24360-110; ECHO-110 (Other Identifier: Incyte Corporation)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No