A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

Study Overview
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Brief Summary
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The purpose of this study is to explore the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of INCB024360 administered in combination with MEDI4736 in subjects with selected advanced solid tumors.

Official Title
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A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

Conditions
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Solid Tumors, Head and Neck Cancer, Lung Cancer, UC (Urothelial Cancer)

Intervention / Treatment
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* Drug: MEDI4736
* Drug: INCB024360


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, age 18 years or older Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment Exclusion Criteria: Laboratory and medical history parameters not within protocol-defined range Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to 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 (exception is tumor types in which a PD-1 pathway targeted agent is approved, e.g. melanoma, non-small cell lung cancer.) Receipt of any anticancer medication in the 21 days prior to receiving the first dose of study medication Has an active or inactive autoimmune process Evidence of interstitial lung disease or active, non-infectious pneumonitis Prior radiotherapy within 2 weeks of initiating treatment; 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 Currently pregnant or breastfeeding

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI4736 + INCB024360<br>MEDI4736 at selected dose levels every 2 weeks + INCB024360 25 mg BID as starting dose, followed by dose escalations until MTD or PAD is identified | Drug: MEDI4736<br>* MEDI4736 administered intravenously (IV) every two weeks (q2w)<br>Drug: INCB024360<br>* INCB024360: Oral daily dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE) | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment | Duration of study treatment and up to 90 days after the last dose [approximately 3 years] | 
| Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Measured every 8 weeks for duration of study treatment [approximately 12 months] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1 | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Measured every 8 weeks for duration of study treatment [approximately 6 months] | 
| Phase 2: Number of Treatment-Emergent Adverse Events | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment | Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years] | 
| Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression | Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression. | Measured every 8 weeks for duration of active study treatment [approximately 24 months] | 
| Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death |  | Measured every 8 weeks for duration of active study treatment [approximately 24 months] | 
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration |  | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | 
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration |  | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | 
| Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve |  | Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1 | 
| Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs) |  | Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks]. |