Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

A Phase II Study of MK-3475 (Pembrolizumab) (NSC #776864) + Epacadostat (NSC #766086) in Recurrent Clear Cell Carcinoma of the Ovary

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03602586
• Other study ID #: NCI-2018-01561
• Secondary ID: NCI-2018-01561NR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 21, 2018
• Est. completion date: September 22, 2024

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well pembrolizumab and epacadostat work in treating patients with ovarian clear cell carcinoma that has come back (recurrent), remains despite treatment (persistent), or is growing, spreading, or getting worse (progressive). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and epacadostat may work better compared to usual treatment (surgery, radiation, or cytotoxic chemotherapy) in treating patients with ovarian clear cell carcinoma.

Description:

PRIMARY OBJECTIVE:

I. To assess the objective tumor response (proportion of objective response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) of the combination of pembrolizumab (MK-3475 [pembrolizumab]) and epacadostat in patients with recurrent or persistent clear cell carcinoma of the ovary.

SECONDARY OBJECTIVES:

I. To determine the nature and degree of toxicity of MK-3475 (pembrolizumab) + epacadostat as assessed by Common Terminology Criteria for Adverse Events (CTCAE) in patients with recurrent or persistent clear cell carcinoma of the ovary.

II. To estimate the progression-free survival (PFS) and overall survival (OS) in patients treated with combination of MK-3475 (pembrolizumab) and epacadostat.

EXPLORATORY TRANSLATIONAL OBJECTIVES:

I. Determine whether the ratio of plasma tryptophan to kynurenine (T:K) correlates with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating plasma T:K pre-treatment, during treatment, and at disease progression.

II. Determine whether the presence of PD-L1, IDO-1, tumor-infiltrating regulatory T cells (Tregs), CD8 tumor-infiltrating lymphocytes (TILs), and human leukocyte antigen (HLA) class I in the tumor microenvironment at baseline correlates with objective response to MK-3475 (pembrolizumab) + epacadostat.

III. Determine whether soluble PD-L1 (sPD-L1) levels in plasma are correlated with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating sPD-L1 concentrations pre-treatment, during treatment, and at disease progression.

OUTLINE:

Patients receive epacadostat orally (PO) twice daily (BID) and pembrolizumab intravenously (IV) over 30 minutes once every 3 weeks (Q3W). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and annually thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: September 22, 2024
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Primary tumors must be at least 50% clear cell histomorphology in order to be eligible or have a histologically documented recurrence with at least 50% clear cell histomorphology. Recurrence should be biopsy proven as per standard of care unless the tumor is located in an area deemed unsafe to biopsy. Histologic confirmation of the original primary tumor is required via the pathology report. The percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report. If slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology, as long as tumor is located in an area deemed safe to biopsy. The percentage of clear cell involvement must be documented in the pathology report or in an addendum to the original report

• All patents must have measurable disease, and at least one "target lesion" to be used to assess response as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Appropriate stage for study entry based on the following diagnostic workup:

• History/physical examination within 28 days prior to registration

• Imaging of target lesions within 28 days prior to registration

• Further protocol-specific assessments

• Recovery from adverse effects of recent surgery, radiotherapy or chemotherapy (residual grade 1 toxicity is considered recovered)

• Any other prior therapy directed at the malignant tumor including chemotherapy, and biologic/targeted agents must be discontinued at least 4 weeks prior to registration. Any hormonal therapy directed at the malignant tumor must be discontinued at least 2 weeks prior to registration

• Any prior radiation therapy must be completed at least 4 weeks prior to registration, and progression must be outside the radiation field

• At least 4 weeks must have elapsed since any major surgery prior to registration

• The trial is open only to women with recurrent or progressive clear cell carcinoma of the ovary

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration

• Patients must have had one prior platinum-based chemotherapy for management of primary disease. Patients are allowed to receive, but are not required to receive, up to two additional cytotoxic regimens for management of recurrent or persistent disease

• Absolute neutrophil count (ANC) >= 1,500/ul (within 14 days prior to registration)

• Platelets >= 100,000/ul (within 14 days prior to registration)

• Hemoglobin (Hgb) >= 8.0 g/dL within 14 days prior to registration (Note: the use of transfusion of other intervention to achieve a Hgb >= 8.0 g/dL is acceptable)

• Creatinine =< 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) >= 60 mL/min using Cockcroft-Gault formula (within 14 days prior to registration)

• Bilirubin =< 2.5 x ULN (within 14 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (within 14 days prior to registration)

• Normal thyroid function testing (thyroid-stimulating hormone [TSH]) (within 14 days prior to registration)

• Negative pregnancy test in women of childbearing potential

• Women of childbearing potential who are sexually active should be willing and able to use medically acceptable forms of contraception for the course of the study through 120 days after the last dose of MK-3475 (pembrolizumab). Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile, who have had a hysterectomy and/or bilateral oophorectomy) do not require contraception

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Patients who have had prior therapy with MK-3475 (pembrolizumab) or epacadostat or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways

• History of severe hypersensitivity reaction to any monoclonal antibody

• Patients with active auto-immune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, and/or epidural disease, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatment. Those with brain metastases are permitted as long as they have been treated with brain radiation therapy and have been documented stability 4 weeks following completion of brain radiation therapy

• In order for patients with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) to be eligible, they must be on a stable highly active antiretroviral therapy (HAART) regimen with no drug-drug interaction with UGT1A9, have CD4+ counts > 350, with no detectable viral load on quantitative polymerase chain reaction (PCR), and no opportunistic infection

• Patients with treated hepatitis viral infections (hepatitis B and C) are eligible if they have completed definitive treatment at least 6 months prior, have no detectable viral load on quantitative PCR, and liver function tests (LFTs) meet eligibility requirements

• Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration

• Therapy with monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitor (SSRIs) within the last 4 weeks or history of serotonin syndrome. Concomitant use of monoamine oxidase inhibitors or SSRIs with epacadostat (INCB024360) is prohibited

• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction and/or who require parenteral hydration and/or nutrition

• Epacadostat (INCB024360) is a substrate of CYP3A4, CYP1A2, CYP2C19, UGT1A9, P-gp, and BCRP. Use caution when administered with strong inhibitors/inducers of these isoenzymes and transporter proteins. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference

• History or presence of an abnormal electrocardiography (ECG) that, in the investigator's opinion, is clinically meaningful. Screening QTc interval > 480 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is > 480 milliseconds, the subject may enroll if the average QTc for the 3 ECGs is < 480 milliseconds. For subjects with an intraventricular conduction delay (QRS interval > 120 msec), the JTc interval may be used in place of the QTc with sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of QTc. Subjects with left bundle branch block are excluded

• Patients who are pregnant or nursing

Related Conditions & MeSH terms

• Carcinoma
• Malignant Ovarian Clear Cell Tumor
• Recurrence
• Recurrent Ovarian Carcinoma

Intervention

Drug:
• Epacadostat
Given PO

Biological:
• Pembrolizumab
Given IV

Locations

Country	Name	City	State
Puerto Rico	Advance Oncology Center	Aguadilla
Puerto Rico	Doctor's Cancer Center-Arecibo	Arecibo
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Hematologia Oncologia San Pablo	Bayamon
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Instituto Oncologia Moderna Ponce	Ponce
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	Primary Care Physician Group	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
Puerto Rico	Centro de Hematologia y Oncologia del Sur	Santa Isabel
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	PCR Oncology	Arroyo Grande	California
United States	Augusta University Medical Center	Augusta	Georgia
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Saint Charles Health System	Bend	Oregon
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Geauga Hospital	Chardon	Ohio
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Coffeyville Regional Medical Center	Coffeyville	Kansas
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle at The Riverfront	Danville	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Western Surgical Care	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Saint Francis Hospital	Federal Way	Washington
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	HaysMed	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Good Samaritan Medical Center	Lafayette	Colorado
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	OhioHealth Mansfield Hospital	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Presbyterian Rust Medical Center/Jorgensen Cancer Center	Rio Rancho	New Mexico
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salina Regional Health Center	Salina	Kansas
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Mercy Hospital Washington	Washington	Missouri
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ratio of Plasma Tryptophan to Kynurenine (T:K)	Will determine whether the ratio of plasma T:K correlates with response to MK-3475 (pembrolizumab) and epacadostat, by evaluating plasma T:K pre-treatment, during treatment, and at disease progression. Pre-treatment levels of T:K ratio in plasma will be assessed for association with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Changes between pre-treatment and post-cycle 1 and changes between post-cycle 1 and disease progression for T:K ratio will be evaluated with paired Student's T tests.	Up to 5 years
Other	Presence of PD-L1, IDO-1, Tumor-infiltrating Regulatory T Cells (Tregs), CD8 Tumor-infiltrating Lymphocytes (TILs), and Human Leukocyte Antigen (HLA) Class I in the Tumor Microenvironment	Will determine whether the presence of PD-L1, IDO-1, Tregs, CD8 TILs, and HLA class I in the tumor microenvironment at baseline correlates with objective response to MK-3475 (pembrolizumab) + epacadostat. Baseline presence of PD-L1, IDO-1, Tregs, TILs, and HLA class I in the tumor microenvironment will also be assessed for correlation with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Will consider logistic regression models for these analyses of continuous biomarkers, if appropriate given the number of responses and if exact tests of response for categorized levels of the biomarkers.	Up to 5 years
Other	Soluble PD-L1 (sPD-L1) Levels in Plasma	Will determine whether sPD-L1 levels in plasma are correlated with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating sPD-L1 concentrations pre-treatment, during treatment, and at disease progression. Pre-treatment levels of sPD-L1 in plasma will be assessed for association with radiographic response to MK-3475 (pembrolizumab) and epacadostat. Changes between pre-treatment and post-cycle 1 and changes between post-cycle 1 and disease progression for sPD-L1 will be evaluated with paired Student's T tests.	Up to 5 years
Primary	Complete or Partial Objective Tumor Response	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria. Exact 95% confidence limits, accounting for interim analysis, will be provided in the final report. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=20% decrease in the sum of the longest diameter of target lesions and a 5 mm absolute increase; Overall Response (OR) = CR + PR.	Within 7 months of study entry
Secondary	Number of Participants With Adverse Events of Grade 3 or Higher	Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. Number of participants with an adverse event of grade 3 or higher.	Adverse events were assessed from the start of treatment until 30 days after the end of the last treatment cycle. Adverse events were collected for a median time of 5.1 months and a maximum time of 23.8 months.
Secondary	Progression-free Survival (PFS)	Disease progression will be defined using RECIST v. 1.1 criteria. The distributions of PFS will be estimated and graphed using the Kaplan-Meier product limit method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=20% decrease in the sum of the longest diameter of target lesions and a 5 mm absolute increase; Overall Response (OR) = CR + PR." Progression-free survival (PFS) is defined as the duration of time from the start of study treatment to time of progression or death, whichever occurs first.	Radiographic tumor assessments were completed 12 weeks after the start of treatment, then every 6 weeks for 49 weeks, followed by every 12 weeks until disease progression or treatment discontinuation. The median follow-up time was 4.8 months.
Secondary	Overall Survival (OS)	Assessment of deaths starting from the time of enrollment.	Overall survival (OS) is defined as the duration of time from the start of study treatment to time of death or the date of last contact. The median follow-up time for OS was 34.9 months.