A Phase 1/2 Study of Azacitidine in Combination With Pembrolizumab and Epacadostat Advanced Solid Tumors including Lung and Colorectal Cancer
- Conditions
- Subjects With Advanced Solid Tumors and Previously Treated Stage IIIB or Stage IV Non–Small Cell Lung Cancer and Stage IV Microsatellite Stable Colorectal CancerMedDRA version: 20.0 Level: PT Classification code 10010035 Term: Colorectal cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000020935MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000016864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004289-25-ES
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 160
•Male or female subjects, age 18 years or older on day of signing
consent.
•Willingness to provide written informed consent for the study.
Part 1 Only
•Subjects with histologically or cytologically confirmed advanced or
metastatic solid tumors that have failed prior standard therapy
Part 2 Only
Note: Subjects must have failed available therapies that are known to
confer clinical benefit as indicated below, unless they are ineligible,
intolerant, or refused standard treatment.
Subjects with histologically or cytologically confirmed NSCLC:
•Stage IIIB or metastatic (Stage IV) NSCLC who have had disease
progression after available therapies for advanced or metastatic disease
that are known to confer clinical benefit, been intolerant to treatment, or
refused standard treatment.
•Prior systemic regimens must include previously approved therapies,
including a platinum-containing chemotherapy regimen; a tyrosine
kinase inhibitor for tumors with driver mutations; and checkpoint
inhibitors where approved
•Must have disease progression on a prior PD-1–pathway targeted agent
(Cohorts A-1, A-3, and A-4).
Subjects with recurrent (unresectable) or metastatic CRC:
•Histologically or cytologically confirmed adenocarcinoma of the
colon/rectum
•Confirmed MSS CRC as per local testing.
•Stage IV MSS CRC who have had disease progression after available
therapies for advanced or metastatic disease that are known to confer
clinical benefit, been intolerant to treatment, or refused standard
treatment.
•Prior systemic regimens must include previously approved therapies,
including fluoropyrimidine-, oxaliplatin-, and irinotecan-based
chemotherapy; an anti–VEGF therapy (if no contraindication); and if
negative for KRAS, NRAS and BRAF mutations and no contraindication,
an anti-EGFR therapy; and progressed after the last administration of
approved therapy.
Subjects with HNSCC:
•Histologically confirmed squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx.
Note: Carcinomas of the nasopharynx, salivary gland, or nonsquamous
cell histology are excluded.
• Must have received prior treatment with a platinum-based therapy.
Subjects who relapsed within 6 months of adjuvant therapy, including a platinum-containing regimen, may enroll.
• Must have documented human papilloma virus status.
Subjects with melanoma:
• Histologically or cytologically confirmed melanoma.
• Unresectable Stage III or Stage IV melanoma, as per American Joint
Committee on Cancer staging system not amenable to local therapy.
• Documentation of V600-activating BRAF mutation status or consent to
BRAF.
• V600 mutation testing during the screening period.
• Must not have ocular
Laboratory and medical history parameters not within Protocol-defined range.
- Absolute neutrophil count < 1.5 × 109/L.
- Platelet count < 100 × 109/L.
- Hemoglobin < 8 g/dL (transfusion is acceptable to meet this criterion).
- Serum creatinine > or = 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 CrCl) < 50 mL/min for subjects with creatinine levels > 1.5 × institutional ULN).
- Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase > or = 2.5 × ULN.
- Total bilirubin > or = 1.2 × ULN are excluded unless direct bilirubin is < or = ULN.
- International normalized ratio or prothrombin time > 1.5 × ULN.
- Activated partial thromboplastin time > 1.5 × ULN.
Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:
- < 14 days for chemotherapy, targeted small-molecule therapy, or radiation therapy.
- < 14 days for a prior PD-1 pathway–targeted agent.
- < 28 days for prior monoclonal antibody used for anticancer therapy with the exception of PD-1 pathway–targeted agents.
- < 14 days for an immune-suppressive–based treatment for any reason
- < 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices.
- Has not recovered from toxic effect(s) of prior therapy to < or = Grade 1.
- Subjects with prior ocular toxicity from prior immune therapy are excluded.
- Subjects who have not recovered adequately from toxicity and/or complications from surgical intervention before starting therapy.
- Subjects who have 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
- Known active CNS metastases and/or carcinomatous meningitis.
- Has received a live vaccine within 30 days of planned start of study therapy.
- Evidence of interstitial lung disease or active, noninfectious pneumonitis.
- History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
- Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy.
- Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
- Subject has a known history of or is positive for hepatitis B or hepatitis C
- Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).
- Active infection requiring systemic therapy.
- Known allergy or reaction to any component of the study drugs or formulation components.
- Women who are pregnant or breastfeeding.
- Known additional malignancy that is progressing
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method