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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Epacadostat
* Drug: Nivolumab
* Drug: Ipilimumab
* Drug: Lirilumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Ipilimumab<br>* Ipilimumab at the protocol-specified dose and schedule.<br>* Other names: BMS-734016;|
| Experimental: Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Ipilimumab<br>* Ipilimumab at the protocol-specified dose and schedule.<br>* Other names: BMS-734016;|
| Experimental: Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Lirilumab<br>* Lirilumab at the protocol-specified dose and schedule.<br>* Other names: BMS-986015;|
| Experimental: Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Lirilumab<br>* Lirilumab at the protocol-specified dose and schedule.<br>* Other names: BMS-986015;|
| Experimental: Phase 2: Dose Expansion: Treatment Group A: Cohort A1<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Ipilimumab<br>* Ipilimumab at the protocol-specified dose and schedule.<br>* Other names: BMS-734016;|
| Experimental: Phase 2: Dose Expansion: Treatment Group A: Cohort A2<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Ipilimumab<br>* Ipilimumab at the protocol-specified dose and schedule.<br>* Other names: BMS-734016;|
| Experimental: Phase 2: Dose Expansion: Treatment Group B: Cohort B1<br>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<br>* Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.<br>* Other names: INCB024360;Drug: Nivolumab<br>* Nivolumab at the protocol-specified dose and schedule.<br>* Other names: BMS-936558;Drug: Lirilumab<br>* Lirilumab at the protocol-specified dose and schedule.<br>* Other names: BMS-986015;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epacadostat, nivolumab, ipilimumab, lirilumab, solid tumor, melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), IDO inhibitor