INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

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 INCAGN01876 when given in combination with immune therapies.

Official Title
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A Phase 1/2 Safety and Efficacy Study of INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

Conditions
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Advanced Malignancies, Metastatic Cancer

Intervention / Treatment
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* Drug: INCAGN01876
* Drug: Epacadostat
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. Phase 1: Subjects with advanced or metastatic solid tumors. Phase 1: Subjects who have disease progression after treatment with available therapies. Phase 2: Subjects with advanced or metastatic melanoma, RCC, and urothelial carcinoma. Presence of measurable disease based on RECIST v1.1. Eastern Cooperative Oncology Group performance status of 0 or 1. Exclusion Criteria: Laboratory and medical history parameters not within the Protocol-defined range Prior treatment with any tumor necrosis factor super family agonist. Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy. Active autoimmune disease. Known active central nervous system metastases and/or carcinomatous meningitis. Evidence of active, noninfectious pneumonitis or history of interstitial lung disease. Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation. Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

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: INCAGN01876 + Pembrolizumab + Epacadostat<br>INCAGN01876 in combination with pembrolizumab and epacadostat | Drug: INCAGN01876<br>* In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose and schedule according to cohort and treatment group enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.<br>Drug: Epacadostat<br>* Epacadostat will be self-administered orally at the protocol-defined dose.<br>* Other names: INCB024360;Drug: Pembrolizumab<br>* Pembrolizumab will be administered IV at the protocol-defined dose.<br>* Other names: Keytruda®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] | A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment. | Screening through 60 days after end of treatment, up to approximately 18 months | 
| Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST | Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1. | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | 
| Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1 | Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1 | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST | Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1. | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months. | 
| Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST | Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause. | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | 
| Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST | Defined as time from first report of SD or better until disease progression or death from any cause. | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | 
| Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST | Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause. | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | 
| Phase 1 & Phase 2: Overall Survival | Defined as the time from the start of combination therapy until death due to any cause. | At 1 year and 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, endometrial cancer, gastric cancer (including stomach and gastroesophageal junction (GEJ)), esophageal cancer, hepatocellular carcinoma (HCC), melanoma (mucosal or cutaneous), Merkel cell carcinoma, mesothelioma, microsatellite instability-high (MSI-H), solid tumors, non-small cell lung cancer (NSCLC), ovarian cancer, squamous cell carcinoma of the head and neck (SCCHN), small cell lung cancer (SCLC), renal cell carcinoma (RCC), triple-negative breast cancer (TNBC), urothelial carcinoma, glucocorticoid-induced tumor necrosis factor receptor (GITR)