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

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03347123
• Collaborator: (none)
• Enrollment: 11
• Locations: 5
• Arms: 7
• Actual Duration (Months): 34.3
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab; Drug: Lirilumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Mar 21, 2018
• Actual Primary Completion Date: Jan 29, 2021
• Actual Study Completion Date: Jan 29, 2021

Arms and Interventions

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: Opdivo® BMS-936558 ; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: Yervoy® BMS-734016
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: Opdivo® BMS-936558 ; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: Yervoy® BMS-734016
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: Opdivo® BMS-936558 ; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: IPH2102 BMS-986015
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: Opdivo® BMS-936558 ; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: IPH2102 BMS-986015
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: Opdivo® BMS-936558 ; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: Yervoy® BMS-734016
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: Opdivo® BMS-936558 ; Drug: Ipilimumab; Ipilimumab at the protocol-specified dose and schedule.; Other Names: Yervoy® BMS-734016
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: Opdivo® BMS-936558 ; Drug: Lirilumab; Lirilumab at the protocol-specified dose and schedule.; Other Names: IPH2102 BMS-986015

Outcome Measures

Primary Outcome Measures

1. Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs) [Screening through up to 100 days after end of treatment, up to approximately 24 months]

   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.

2. Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

Secondary Outcome Measures

1. Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1 [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

2. Phase 1: Duration of Response (DOR) [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

3. Phase 1: Progression-free Survival (PFS) [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

4. Phase 2: Duration of Response (DOR) [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

5. Phase 2: Progression-free Survival (PFS) [Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)]

   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.

6. Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) [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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
3	John Wayne Cancer Institute	Santa Monica	California	United States	90404
4	Duke University Medical Center	Durham	North Carolina	United States	27710
5	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Incyte Corporation

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 5, 2018

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03347123
• Other Study ID Numbers: INCB 24360-208 (ECHO-208); 2017-001743-12
• First Posted: Nov 20, 2017
• Last Update Posted: Feb 28, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Epacadostat; nivolumab; ipilimumab; lirilumab; solid tumor; melanoma; non-small cell lung cancer (NSCLC); squamous cell carcinoma of the head and neck (SCCHN); IDO inhibitor
• Additional relevant MeSH terms: Neoplasms; Nivolumab; Ipilimumab

Study Results

Participant Flow

Recruitment Details

Participants took part at 4 study centers in the United States from 21 March 2018 to 29 January 2021.

Pre-assignment Detail

Participants were to be enrolled in Phase 1: Dose escalation Phase which consisted of 2 Treatment Groups: A (epacadostat, nivolumab, ipilimumab) and B (epacadostat, nivolumab and lirilumab), followed by Phase 2: a tumor-specific cohort Dose expansion Phase, which was to begin when maximum tolerated dose (MTD)/pharmacologically active dose (PAD) of epacadostat was determined in Phase 1. However, the study was terminated prior to enrollment in Phase 1: Treatment Group B and Phase 2 cohorts.

Arm/Group Title	Phase 1: Dose Escalataion: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID	Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID	Phase 2: Dose Expansion: Treatment Group A: Cohort A1	Phase 2: Dose Expansion: Treatment Group A: Cohort A2	Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.
Period Title: Overall Study
STARTED	5	6	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	5	6	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	5	6	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.4 (8.79)	53.8 (8.57)	59.1 (10.20)
Sex: Female, Male (Count of Participants)
Female	2 40%	3 50%	5 45.5%
Male	3 60%	3 50%	6 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 60%	5 83.3%	8 72.7%
Unknown or Not Reported	2 40%	1 16.7%	3 27.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 16.7%	1 9.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	5 83.3%	10 90.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	90.464 (16.3665)	81.255 (26.5702)	85.441 (21.9832)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	173.2 (9.20)	174.2 (3.25)	173.7 (6.28)

Outcome Measures

1. Primary Outcome

Title	Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Screening through up to 100 days after end of treatment, up to approximately 24 months

Outcome Measure Data

Analysis Population Description

Safety population included all participants enrolled in the study who received at least 1 dose of combination therapy. Treatment group B was excluded from this analysis as no participants were enrolled.

Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Arm/Group Description	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.	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.
Measure Participants	5	6
Number [percentage of participants]	100 2000%	100 1666.7%

2. Primary Outcome

Title	Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 2: Dose Expansion: Treatment Group A: Cohort A1	Phase 2: Dose Expansion: Treatment Group A: Cohort A2	Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

3. Secondary Outcome

Title	Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Arm/Group Description	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.	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.
Measure Participants	0	0

4. Secondary Outcome

Title	Phase 1: Duration of Response (DOR)
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Arm/Group Description	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.	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.
Measure Participants	0	0

5. Secondary Outcome

Title	Phase 1: Progression-free Survival (PFS)
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID	Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID
Arm/Group Description	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.	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.
Measure Participants	0	0

6. Secondary Outcome

Title	Phase 2: Duration of Response (DOR)
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 2: Dose Expansion: Treatment Group A: Cohort A1	Phase 2: Dose Expansion: Treatment Group A: Cohort A2	Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Phase 2: Progression-free Survival (PFS)
Description	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.
Time Frame	Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 2: Dose Expansion: Treatment Group A: Cohort A1	Phase 2: Dose Expansion: Treatment Group A: Cohort A2	Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

8. Secondary Outcome

Title	Phase 2: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

As the study was terminated early due to business decision, with lack of enrollment, the data for this outcome measure was not collected and analyzed as planned.

Arm/Group Title	Phase 2: Dose Expansion: Treatment Group A: Cohort A1	Phase 2: Dose Expansion: Treatment Group A: Cohort A2	Phase 2: Dose Expansion: Treatment Group B: Cohort B1
Arm/Group Description	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.	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.	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.
Measure Participants	0	0	0

Adverse Events

Time Frame	Screening through up to 100 days after end of treatment, up to approximately 24 months
Adverse Event Reporting Description	Safety population included all participants enrolled in the study who received at least 1 dose of combination therapy.
Arm/Group Title	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID		Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID		Total
Arm/Group Description	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.		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.		Total
All Cause Mortality
	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID		Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		2/6 (33.3%)		3/11 (27.3%)
Serious Adverse Events
	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID		Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		3/6 (50%)		5/11 (45.5%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Cardiac disorders
Acute myocardial infarction	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Atrial fibrillation	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Gastrointestinal disorders
Diarrhoea	0/5 (0%)	0	1/6 (16.7%)	2	1/11 (9.1%)	2
Duodenitis	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Pancreatitis	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
General disorders
Multiple organ dysfunction syndrome	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Pain	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Infections and infestations
Lung infection	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Metabolism and nutrition disorders
Dehydration	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Hypokalaemia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Polyarthritis	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Respiratory failure	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID		Phase 1: Dose Esclataion: Treatment Group A: Cohort 2 Epacadostat 100 mg BID		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		6/6 (100%)		11/11 (100%)
Blood and lymphatic system disorders
Anaemia	1/5 (20%)	1	1/6 (16.7%)	1	2/11 (18.2%)	2
Iron deficiency anaemia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Cardiac disorders
Atrial fibrillation	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Supraventricular tachycardia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Endocrine disorders
Hyperthyroidism	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Hypopituitarism	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Hypothyroidism	2/5 (40%)	2	2/6 (33.3%)	2	4/11 (36.4%)	4
Eye disorders
Diplopia	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Gastrointestinal disorders
Abdominal pain	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Abdominal pain upper	0/5 (0%)	0	1/6 (16.7%)	2	1/11 (9.1%)	2
Ascites	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Autoimmune pancreatitis	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Constipation	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Diarrhoea	3/5 (60%)	7	1/6 (16.7%)	1	4/11 (36.4%)	8
Nausea	1/5 (20%)	1	1/6 (16.7%)	1	2/11 (18.2%)	2
Vomiting	1/5 (20%)	1	1/6 (16.7%)	1	2/11 (18.2%)	2
General disorders
Fatigue	2/5 (40%)	2	1/6 (16.7%)	1	3/11 (27.3%)	3
Influenza like illness	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Pyrexia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Infections and infestations
Bacteraemia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Bronchitis	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Herpes zoster	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Staphylococcal infection	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Urinary tract infection	1/5 (20%)	1	2/6 (33.3%)	2	3/11 (27.3%)	3
Injury, poisoning and procedural complications
Procedural pain	1/5 (20%)	2	1/6 (16.7%)	1	2/11 (18.2%)	3
Seroma	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Investigations
Alanine aminotransferase increased	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Amylase increased	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Aspartate aminotransferase increased	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Blood alkaline phosphatase increased	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Lipase increased	2/5 (40%)	2	1/6 (16.7%)	2	3/11 (27.3%)	4
Weight decreased	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Metabolism and nutrition disorders
Decreased appetite	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Dehydration	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Hypocalcaemia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Hypokalaemia	2/5 (40%)	2	1/6 (16.7%)	1	3/11 (27.3%)	3
Hypomagnesaemia	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Hyponatraemia	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Malnutrition	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/5 (40%)	2	0/6 (0%)	0	2/11 (18.2%)	2
Arthritis	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Joint swelling	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Osteoarthritis	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Synovial cyst	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Psychiatric disorders
Depression	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Renal and urinary disorders
Micturition urgency	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Reproductive system and breast disorders
Breast pain	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Pruritus	1/5 (20%)	1	2/6 (33.3%)	3	3/11 (27.3%)	4
Pruritus generalised	1/5 (20%)	1	2/6 (33.3%)	2	3/11 (27.3%)	3
Rash	2/5 (40%)	2	1/6 (16.7%)	1	3/11 (27.3%)	3
Rash generalised	1/5 (20%)	1	1/6 (16.7%)	1	2/11 (18.2%)	2
Rash maculo-papular	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1
Vitiligo	1/5 (20%)	1	0/6 (0%)	0	1/11 (9.1%)	1
Vascular disorders
Hypotension	0/5 (0%)	0	1/6 (16.7%)	1	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.