A Phase 1/2 Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors

Phase 1

• Conditions: Subjects with solid tumors of the type of colorectal cancer, pancreatic ductal adenocarcinoma, Squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, any solid tumor that progressed on previous therapy with a PD-1 or PD-L1 inhibitor, urothelial carcinoma or squamous cell carcinoma of the head and neck; MedDRA version: 20.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10051971Term: Pancreatic adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004678-16-ES
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-19
• Last Update Posted: 19 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 421

Inclusion Criteria

• Men or women aged 18 years or older.
• Presence of measurable disease per RECIST v1.1. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measureable if progression has been demonstrated in the lesion.
• ECOG performance status of 0 or 1.
• Willing to avoid pregnancy or fathering children from screening through 120 days after the last dose of epacadostat and pembrolizumab based on criteria defined in the body of the Protocol.
Phase 1 subjects only:
• Subjects with locally advanced or metastatic solid tumors who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or subjects who refuse standard treatment. Locally advanced disease must not be amenable to resection with curative intent.
• Subjects must not have received therapy with an IDO inhibitor.
Phase 2 CRC subjects only:
• Histologically or cytologically confirmed advanced or metastatic adenocarcinoma of the colon or rectum.
• Subjects must not have received previous chemotherapy as first-line therapy for advanced or metastatic disease.
• Subjects must not have received previous immune checkpoint inhibitors (eg, cytotoxic T-lymphocyte–associated protein 4 [CTLA-4] inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
Phase 2 PDAC subjects only:
• Histologically or cytologically confirmed advanced or metastatic PDAC.
• Subjects must not have received previous chemotherapy as first-line therapy for advanced or metastatic disease.
• Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
Phase 2 squamous or nonsquamous NSCLC subjects only:
• Histologically or cytologically confirmed Stage IIIB, Stage IV, or recurrent squamous or nonsquamous NSCLC.
• Subjects without driver mutations (eg, BRAF or epidermal growth factor receptor [EGFR] mutations, anaplastic lymphoma kinase (ALK) fusion oncogene or ROS1 rearrangements) must not have received previous chemotherapy as first-line therapy for Stage IIIB, Stage IV, or recurrent NSCLC.
• Subjects with driver mutations (eg, BRAF or EGFR mutations, ALK fusion oncogene or ROS1 rearrangements) must have received prior treatment only with an approved kinase inhibitor with subsequent disease progression.
• Subjects must not have received previous immune checkpoint inhibitors (eg, CTLA-4 inhibitor, PD-1 inhibitor, PD-L1 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation), and/or an IDO inhibitor.
Phase 2 subjects in the cohort of subjects with any solid tumor that progressed on previous therapy with a PD-1 or PD-L1 inhibitor only:
• Histologically or cytologically confirmed advanced or metastatic solid tumors that progressed on previous monotherapy with a PD-1 or PD-L1 inhibitor or previous combination therapy that included a PD-1 or PD-L1 inhibitor.
• Subjects must not have received previous therapy with an IDO inhibitor.
• Subjects may have received previous chemotherapy for advanced or metastatic disease.
Phase 2 subjects in the mandatory biopsy cohort only:
• Willing to undergo pretreatment and on-treatment core or excisional tumor biopsies.
Phase 2 efficacy expansion subjects only:
• W

Exclusion Criteria

• Laboratory and medical history parameters not within the Protocol-defined range. If the screening laboratory tests below were conducted > 7 days before treatment initiation, they will need to be repeated on Cycle 1 Day 1 before initiation of treatment.
- Absolute neutrophil count < 1.5 × 109/L.
- Platelet count < 100 × 109/L.
- Hemoglobin < 9 g/dL or < 5.6 mmol/L.
- Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance) < 50 mL/min for subjects with creatinine levels > 1.5 × institutional ULN.
- Aspartate aminotransferase, alanine aminotransferase (ALT), and alkaline phosphatase = 2.5 × ULN.
- Total bilirubin = 1.2 × ULN.
- International normalized ratio (INR), prothrombin time, and activated partial thromboplastin time (aPTT) > 1.5 × ULN (unless the subject is receiving anticoagulant therapy, in which case the subject may be included as long as the INR, prothrombin time, and aPTT are within therapeutic range of intended use of anticoagulants).
• Receipt of anticancer medications or investigational drugs within the following intervals before Cycle 1 Day 1:
- = 14 days for chemotherapy or targeted small molecule therapy.
- = 28 days for previous monoclonal antibody used for anticancer therapy.
- = 7 days for immune-suppressive–based treatment for any reason.
- = 28 days or 5 half-lives (whichever is longer) before Cycle 1 Day 1 for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.
• Previous radiotherapy within 14 days of Cycle 1 Day 1 (except for radiation to the central nervous system [CNS], which requires a = 28-day washout as described below). Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment.
• Known active CNS metastases and/or carcinomatous meningitis.
• Has not recovered to = Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy.
• Receipt of a live vaccine within 30 days of planned start of study therapy.
• Active infection requiring systemic therapy.
• Subjects who have any active or inactive autoimmune disease or syndrome (ie, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• History of (noninfectious) pneumonitis that required steroids or current pneumonitis or interstitial lung disease.
• History of organ transplant that requires use of immunosuppressive therapy, has a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone or its equivalent) or any other form of immunosuppressive therapy within 7 days before Cycle 1 Day 1.
Known history of or screening test is positive for hepatitis B virus (HBV; eg, HBsAg reactive or HBV DNA detected) or hepatitis C virus (HCV; HCV antibody positive and/or HCV RNA qualitative is detected).
• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
• History or presence of an ECG that, in the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified