A Phase 1/2, Open-Label, Dose-Rising , Safety, Tolerability, and Efficacy Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or MetastaticCancers (ECHO-208)

Phase 1

• Conditions: Phase 1 (Dose Escalation): Advanced or metastatic solid tumors.Phase 2 (Dose Expansion): Advanced or metastatic non–small cell lung cancer (NSCLC), unresectable or metastatic melanoma (MEL) and recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).; MedDRA version: 20.0Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10050017Term: Lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027150Term: Melanoma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10071540Term: Head and neck cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, mal

• Registration Number: EUCTR2017-001743-12-GB
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-11-23
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

Phase 1 only:
• Subjects with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have disease progression on or after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment.
Phase 2:
Cohort A1 (MEL):
• Subjects with histologically confirmed unresectable Stage III or Stage IV MEL not amenable to local therapy who have received no prior systemic treatment (excluding adjuvant or neoadjuvant chemotherapy) for advanced or metastatic disease. Mucosal or cutaneous MEL is acceptable; however, subjects with ocular MEL are excluded.
- Must have documentation of BRAF mutation status.
Cohort A2 (NSCLC):
• Subjects with histologically or cytologically confirmed Stage IIIB, Stage IV, or recurrent squamous or nonsquamous NSCLC and who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease.
- Subjects with known driver mutations (including EGFR or BRAF mutations, or ALK or ROS1 rearrangements) are excluded.
- Prior adjuvant or neoadjuvant chemotherapy completed less than 6 months before study entry will be counted as 1 prior line of therapy.
Cohort B1 (SCCHN):
• Subjects with histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that is not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy) and who have received no more than 1 prior line of platinum-based chemotherapy for recurrentor metastatic disease.
- Must have documentation of human papillomavirus status (eg, p16 status) of tumor (oropharyngeal only).
- Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or nonsquamous histologies are excluded.
Phase 2 (all cohorts):
• Willingness to undergo serial pretreatment and on-treatment core or excisional tumor biopsies.
All subjects (Phase 1 and 2):
• Ability to comprehend and willingness to sign an informed consent form.
• 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 locoregional therapy, are considered measurable if progression has been demonstrated in the lesion following such therapy.
• ECOG performance status of 0 or 1.
• Expected survival of = 12 weeks.
• Willingness and ability to comply with the scheduled visits, treatment plan, and laboratory tests.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 71

Exclusion Criteria

• Laboratory and medical history parameters not within the Protocol-defined range; all screening laboratory tests should be performed within 7 days of Cycle 1 Day 1.
- Absolute neutrophil count < 1.5 × 109/L.
- Platelets < 100 × 109/L.
- Hemoglobin < 9 g/dL or < 5.6 mmol/L (transfusion is acceptable to meet this criterion).
- Serum creatinine = 1.5 × institutional ULN, or measured or calculated creatinine clearance (CrCl) < 50 mL/min for subjects with creatinine levels > 1.5 × institutional ULN (glomerular filtration rate can also be used in place of CrCl).
- Phase 1 only: AST or ALT = 1.5 × institutional ULN.
- Phase 2 only: AST or ALT = 2.5 × institutional ULN.
- Total bilirubin = 1.5 × institutional ULN or conjugated (direct) bilirubin = institutional ULN.
- International normalized ratio or prothrombin time > 1.5 × institutional ULN.
- Activated partial thromboplastin time > 1.5 × institutional ULN unless subject is receiving anticoagulant therapy, as long as PTT is within therapeutic range of intended use of anticoagulants.
- Phase 1 only: Albumin = 3.0 g/dL or with medical monitor approval.
• Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:
- = 21 days for chemotherapy or targeted small-molecule therapy
- = 28 days for previous monoclonal antibody used for anticancer therapy.
- = 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 7 days of Cycle 1 Day 1 (except for radiation to CNS, which requires a = 28-day washout). 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.
• Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.
• Any unresolved toxicity > Grade 1 from previous anticancer therapy, except for stable chronic toxicities not expected to resolve
• Subjects who are receiving an immunologically based treatment for any reason, including chronic use of systemic steroid or at doses = 10 mg/day prednisone equivalent within 7 days before the first dose of study drug.
• Receipt of a live vaccine within 30 days of planned start of study therapy.
• Active infection requiring systemic therapy.
• Subjects with any active or inactive autoimmune disease or syndrome 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).
• Evidence of interstitial lung disease or active, noninfectious pneumonitis, including symptomatic and/or pneumonitis requiring treatment.
• History of organ transplant that requires use of immunosuppressive therapy.
• Has known history of or is positive for hepatitis B (hepatitis B surface antigen [HbsAg] reactive) or hepatitis C.
- Hepatitis B virus DNA must be undetectable and HBsAg negative at the screening visit.
- Hepatitis C antibody testing is allowed for screening purposes where HCV RNA is not standard of care.
- Subjects who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at the s

Study & Design

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