A Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Participants With Advanced or Metastatic Malignancies (ECHO-208)

A Phase 1/2, Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)

The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab; Drug: Lirilumab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• During Phase 1, participant with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment.
• During Phase 2, participant with advanced cancer who have received at least one prior therapy or are treatment naive, depending on the specified tumor type.
• Presence of measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of ≥ 12 weeks.

Exclusion Criteria:

• Laboratory and medical history parameters not within the Protocol-defined range.
• Receipt of anticancer medications or investigational drugs within Protocol-defined time frames.
• Previous radiotherapy within 7 days of Cycle 1 Day 1.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.
• Active infection requiring systemic therapy.
• Any active or inactive autoimmune disease or syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID; Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: BMS-734016; Yervoy®
EXPERIMENTAL: Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID; Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: BMS-734016; Yervoy®
EXPERIMENTAL: Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID; Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: BMS-986015; IPH2102
EXPERIMENTAL: Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID; Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: BMS-986015; IPH2102
EXPERIMENTAL: Phase 2: Dose Expansion: Treatment Group A: Cohort A1; Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: BMS-734016; Yervoy®
EXPERIMENTAL: Phase 2: Dose Expansion: Treatment Group A: Cohort A2; Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: BMS-734016; Yervoy®
EXPERIMENTAL: Phase 2: Dose Expansion: Treatment Group B: Cohort B1; Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.	Drug: Epacadostat; Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.; Other Names: INCB024360; Drug: Nivolumab; Nivolumab at the protocol-specified dose and schedule.; Other Names: BMS-936558; Opdivo®; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: BMS-986015; IPH2102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)	A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.	Screening through up to 100 days after end of treatment, up to approximately 24 months
Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1	ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Phase 1: Duration of Response (DOR)	DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Phase 1: Progression-free Survival (PFS)	PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Phase 2: Duration of Response (DOR)	DOR was defined as the time from the earliest date of CR or PR until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Phase 2: Progression-free Survival (PFS)	PFS was defined as the time from the start of combination therapy until the earliest date at which progression criteria are met as determined by investigator evaluation of radiographic disease assessment per RECIST v1.1, or date of death due to any cause. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)
Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)	A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.	Screening through up to 100 days for treatment Group A and 150 days for treatment Group B after end of treatment, up to approximately 24 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Medical Monitor Consultant for Incyte, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2018
• Primary Completion (ACTUAL): January 29, 2021
• Study Completion (ACTUAL): January 29, 2021

Study Registration Dates

• First Submitted: November 14, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (ACTUAL): November 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: solid tumor; melanoma; nivolumab; Epacadostat; ipilimumab; non-small cell lung cancer (NSCLC); squamous cell carcinoma of the head and neck (SCCHN); lirilumab; IDO inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: INCB 24360-208 (ECHO-208); 2017-001743-12 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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