Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Cancer of Head and Neck Carcinoma, Squamous Cell of Head and Neck Head and Neck Cancer Neoplasms, Head and Neck Squamous Cell Carcinoma of the Head and Neck Squamous Cell Carcinoma, Head and Neck	Biological: MK-3475 (neoadjuvant) Other Names SCH 900475 Pembrolizumab Keytruda Procedure: Surgery Other Names Radiation: Intensity modulated radiation therapy Other Names IMRT Radiation: Image-guided radiation therapy Other Names IGRT Drug: Cisplatin Other Names cis-DDP cis-Platinum II cis-Diamminedichloroplatinum DDP Biological: MK-3475 (adjuvant) Other Names SCH 900475 Pembrolizumab Keytruda Procedure: Peripheral blood Other Names	Phase 2

Tracking Information

First Submitted Date	November 17, 2014
Last Update Posted Date	February 08, 2018
Actual Start Date	March 25, 2015
Anticipated Completion Date	March 31, 2023
Actual Primary Completion Date	March 31, 2020
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Locoregional recurrence rates in Cohorts 1 and 2 [Time Frame: 1 year]

• Distant failure rate in Cohorts 1 and 2 [Time Frame: 1 year]

• Rate of major pathologic treatment effect in Cohort 1 [Time Frame: After one dose of neoadjuvant MK-3475]

• Rate of major pathologic treatment effect in Cohort 2 [Time Frame: After two doses of neoadjuvant MK-3475]

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Occurrence of adverse events in Cohorts 1 and 2 [Time Frame: 90 days after last dose of MK-3475]

  Reportable adverse events will be tracked for 30 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events thought to be possibly, probably, or definitely related to MK-3475. Events thought to be probably or definitely related to surgery, adjuvant chemotherapy, or radiotherapy need not be recorded. Please note that patients must be followed for events of clinical interest for 90 days following the last day of study treatment.

• Surgical complications and/or delays in Cohorts 1 and 2 [Time Frame: At the time of surgery (approximately 2-3 weeks after registration)]

• Rate of locoregional recurrences (LRR) in Cohorts 1 and 2 [Time Frame: 1 year]

• Rate of distant metastases (DM) in Cohorts 1 and 2 [Time Frame: 1 year]

Original Secondary Outcome Measures

Study Design

Brief Title	Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma
Official Title	Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma
Brief Summary	The goal of this trial is to test the ability of MK-3475 (pembrolizumab) to improve locoregional recurrence and distant metastatic rates in high-risk patients with locally advanced head and neck squamous cell carcinomas (HNSCCs) that are treated with current standard of care surgical approaches.
Detailed Description
Study Type	Interventional
Study Phase	Phase 2
Estimated Enrollment	66
Allocation	Non-Randomized
Interventional Model	Sequential Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Conditions	Cancer of Head and Neck Carcinoma, Squamous Cell of Head and Neck Head and Neck Cancer Neoplasms, Head and Neck Squamous Cell Carcinoma of the Head and Neck Squamous Cell Carcinoma, Head and Neck
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Biological: MK-3475 (neoadjuvant) Other Names SCH 900475 Pembrolizumab Keytruda Procedure: Surgery Standard of care Other Names Radiation: Intensity modulated radiation therapy Recommended, standard of care Other Names IMRT Radiation: Image-guided radiation therapy Recommended, standard of care Other Names IGRT Drug: Cisplatin Standard of care Other Names cis-DDP cis-Platinum II cis-Diamminedichloroplatinum DDP Biological: MK-3475 (adjuvant) Other Names SCH 900475 Pembrolizumab Keytruda Procedure: Peripheral blood -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery Other Names
Study Groups/Cohorts	Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery
Study Arms	Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Biological : MK-3475 (neoadjuvant) Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Procedure : Surgery Standard of care Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Radiation : Intensity modulated radiation therapy Recommended, standard of care Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Radiation : Image-guided radiation therapy Recommended, standard of care Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Drug : Cisplatin Standard of care Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Biological : MK-3475 (adjuvant) Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less. Procedure : Peripheral blood -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Procedure : Peripheral blood -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Drug : Cisplatin Standard of care Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Radiation : Image-guided radiation therapy Recommended, standard of care Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Radiation : Intensity modulated radiation therapy Recommended, standard of care Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Procedure : Surgery Standard of care Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery Biological : MK-3475 (neoadjuvant)

Arm	Intervention/Treatment
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Biological : MK-3475 (neoadjuvant)
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Procedure : Surgery Standard of care
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Radiation : Intensity modulated radiation therapy Recommended, standard of care
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Radiation : Image-guided radiation therapy Recommended, standard of care
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Drug : Cisplatin Standard of care
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Biological : MK-3475 (adjuvant)
Experimental Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475 MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery. Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of: risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions) optional image-guided radiation therapy risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based on 's surgical pathology from standard of care surgery shows high risk features (positive margins or extracapsular extension). These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.	Procedure : Peripheral blood -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Procedure : Peripheral blood -Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Drug : Cisplatin Standard of care
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Radiation : Image-guided radiation therapy Recommended, standard of care
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Radiation : Intensity modulated radiation therapy Recommended, standard of care
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Procedure : Surgery Standard of care
Experimental Cohort 2: Neoadjuvant MK-3475 -MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery	Biological : MK-3475 (neoadjuvant)

Recruitment Information

Recruitment Status:	Recruiting
Enrollment	66
Completion Date	March 31, 2023
Eligibility Criteria:	Inclusion Criteria: - Histologically or cytologically confirmed stage III or IV HNSCC oral cavity, hypopharynx, oropharynx, larynx (excluding p16 or HPV-positive oropharynx primaries and sinonasal primaries). - Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1. - At least 18 years of age. - ECOG performance status ≤ 1 - Normal bone marrow and organ function as defined below: - Absolute neutrophil count ≥ 1,500/mcl - Platelets ≥ 100,000/mcl - Hemoglobin ≥ 9 g/dL - Total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN - AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver metastases) - Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN - INR ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants - aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as INR or PTT is within therapeutic range of intended use of anticoagulants - Sexually active women of childbearing potential and men must agree to use 2 methods of contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 120 days after last dose of MK-3475. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. - Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: - Prior treatment for head and neck cancer. - Patients with HPV-positive or p16-positive oropharyngeal SCCA. - Patients with sinonasal SCCAs - Patients with metastatic SCCA neck disease with an unknown primary tumor site - Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). - Received a live vaccine within 30 days prior to the first dose of MK-3475. - A history of other malignancy ≤ 3 years previous with the exception of previous head and neck cancer treated only by surgery, basal cell or squamous cell carcinoma of the skin which were treated with local resection only, or carcinoma in situ of the cervix. Note: patients with synchronous head and neck cancer primaries are an exception to this criterion and may qualify for the study. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of MK-3475. - Currently receiving any other investigational agents or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of MK-3475. - A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 or other agents used in the study. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements. - Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. - Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test within 72 hours of study entry. - Known history of active TB (bacillus tuberculosis). - Known active hepatitis B (e.g. HBsAg reactsive) or hepatitis C (e.g. HCV RNA [qualitative] is detected). - Known history of HIV (HIV 1/2 antibodies).
Gender	All
Age	18 Years to N/A
Accepts Healthy Volunteers	No
Contacts	Douglas R Adkins, M.D. 314-362-4471 [email protected]
Listed Location Countries	United States

Administrative Information

NCT Number:	NCT02296684
Other Study ID Numbers	201412118
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Washington University School of Medicine
Collaborators	Merck Sharp & Dohme Corp.
Investigators	Principal Investigator Douglas R Adkins, M.D. Washington University School of Medicine