ClinicalTrials.gov
ClinicalTrials.gov Menu

Azacitidine Combined With Pembrolizumab and Epacadostat in Subjects With Advanced Solid Tumors (ECHO-206)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02959437
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
This is an open-label, Phase 1/2 study in subjects with advanced or metastatic solid tumors. The study has three separate treatment groups where separate epigenetic agents are evaluated with an immunotherapy combination. Treatment Group A will evaluate the DNA methyltransferase inhibitor azacitidine in combination with the programmed death receptor-1 (PD-1) inhibitor pembrolizumab and the indoleamine 2,3-dioxygenase (IDO-1) inhibitor epacadostat; Treatment Group B will evaluate the bromodomain and extra-terminal (BET) inhibitor INCB057643 with pembrolizumab and epacadostat; and Treatment Group C will evaluate the lysine-specific demethylase 1A (LSD1) inhibitor INCB059872 with pembrolizumab and epacadostat. The study will be divided into 2 parts (Part 1 and 2). Part 1 is a dose-escalation assessment to evaluate the safety and tolerability of the combination therapies. Once the recommended doses have been determined, subjects with previously treated NSCLC, microsatellite-stable colorectal cancer (CRC), head and neck squamous cell carcinoma, urothelial carcinoma, and melanoma will be enrolled into expansion cohorts in Part 2.

Condition or disease Intervention/treatment Phase
Solid Tumors Advanced Malignancies Metastatic Cancer Drug: Azacitidine Drug: Pembrolizumab Drug: Epacadostat Drug: INCB057643 Drug: INCB059872 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 531 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of Azacitidine in Combination With Pembrolizumab and Epacadostat in Subjects With Advanced Solid Tumors and Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Stage IV Microsatellite-Stable Colorectal Cancer (ECHO-206)
Actual Study Start Date : January 24, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Treatment Group A: Azacitidine + Pembrolizumab + Epacadostat
Part 1 is an open-label 3 + 3 + 3 dose-escalation design based on observing each dose level for a period of 21 days. Part 2 will evaluate the recommended dose determined in Part 1.
Drug: Azacitidine
Five doses of azacitidine will be administered by subcutaneous injection or intravenously (IV) over Days 1 to 7 in Cycles 1 through 6.
Drug: Pembrolizumab
Pembrolizumab will be administered in a 30-minute IV infusion every 3 weeks on Day 1 of each 21-day cycle.
Drug: Epacadostat
Epacadostat tablets will be administered orally twice daily.
Experimental: Treatment Group B: INCB057643 + Pembrolizumab + Epacadostat
Part 1 is an open-label 3 + 3 + 3 dose-escalation design based on observing each dose level for a period of 42 days. Part 1 will also contain dose-expansion cohorts in previously treated NSCLC and MSS CRC. Part 2 will evaluate the recommended dose determined in Part 1.
Drug: INCB057643
INCB057643 will be orally self- administered once daily beginning on Cycle 1 Day 1 and continuously thereafter in 21-day cycles.
Drug: Pembrolizumab
Pembrolizumab will be administered in a 30-minute IV infusion every 3 weeks of each 21-day cycle starting on Cycle 2 Day 1.
Drug: Epacadostat
Epacadostat tablets will be administered orally twice daily starting at Cycle 2 Day 1.
Experimental: Treatment Group C: INCB059872 + Pembrolizumab + Epacadostat
Part 1 is an open-label 3 + 3 + 3 dose-escalation design based on observing each dose level for a period of 42 days. Part 1 will also contain dose-expansion cohorts in previously treated NSCLC and MSS CRC. Part 2 will evaluate the recommended dose determined in Part 1.
Drug: Pembrolizumab
Pembrolizumab will be administered in a 30-minute IV infusion every 3 weeks of each 21-day cycle starting on Cycle 2 Day 1.
Drug: Epacadostat
Epacadostat tablets will be administered orally twice daily starting at Cycle 2 Day 1.
Drug: INCB059872
INCB059872 will be orally self- administered once daily OR every other day beginning on Cycle 1 Day 1 and continuously thereafter in 21-day cycles.



Primary Outcome Measures :
  1. Part 1: Frequency, duration, and severity of adverse events [ Time Frame: Baseline through 42-49 days after end of treatment, estimated up to 18 months. ]
    A treatment-emergent AE was defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).

  2. Part 2: Objective response rate based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) [ Time Frame: Every 9 weeks for the duration of study participation; estimated to be 18 months. ]
    Defined as the percentage of subjects having a complete response or partial response.


Secondary Outcome Measures :
  1. Part 1: Objective response rate based on RECIST v1.1 [ Time Frame: Every 9 weeks for the duration of study participation; estimated to be 18 months ]
    Defined as the percentage of subjects having a complete response or partial response.

  2. Part 2: Frequency, duration, and severity of adverse events [ Time Frame: Baseline through 42-49 days after end of treatment, estimated up to 18 months. ]
    A treatment-emergent AE was defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).

  3. Parts 1 and 2: Percentage of responders determined by immunohistochemistry [ Time Frame: Baseline and Week 5 or Week 6. ]
    Responder is defined as an increase in the number of tumor-infiltrating lymphocytes or the ratio of CD8+ lymphocytes to T regulatory cells infiltrating tumor post-treatment versus pretreatment with pembrolizumab and epacadostat in combination with azacitidine.

  4. Parts 1 and 2: Progression-free survival based on RECIST v1.1. [ Time Frame: Every 9 weeks for the duration of study participation; estimated to be 18 months. ]
    Defined as the time from date of first dose of study drug until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.

  5. Parts 1 and 2: Duration of response based on RECIST v1.1 [ Time Frame: Every 9 weeks for the duration of study participation; estimated to be 18 months. ]
    Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willingness to provide written informed consent for the study.
  • Willingness to undergo a pretreatment and on-treatment tumor biopsy to obtain tumor tissue.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Part 1: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject refusal or intolerance is also allowable).
  • Part 2:

    *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:

    • Metastatic (Stage IV) or recurrent NSCLC (according to American Joint Committee on Cancer 7th edition guidelines) 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.
  • Subjects with recurrent (unresectable) or metastatic CRC:

    • Have histologically confirmed microsatellite stable (MSS) CRC.
    • Stage IV MSS CRC (according to American Joint Committee on Cancer 7th edition guidelines) 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-epidermal growth factor receptor (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.
    • Carcinomas of the nasopharynx, salivary gland, or nonsquamous cell histology are excluded.
    • Must have received prior treatment with a platinum-based therapy
    • Must have had documented disease progression while on a prior PD-1 pathway-targeted agent.
  • 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.
  • Subjects with urothelial carcinoma:

    • Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, urinary bladder, or urethra that is transitional cell or mixed transitional/nontransitional (predominantly transitional) cell type.
    • Stage IV locally advanced or metastatic urothelial carcinoma (according to American Joint Committee on Cancer 7th edition guidelines) with documented disease progression while on a PD-1 pathway targeted therapy.

Exclusion Criteria:

  • Laboratory parameters not within the protocol-defined range.
  • Receipt of anticancer medications or investigational drugs within a defined interval before the first administration of study drug.
  • Has not recovered from toxic effects of prior therapy to ≤ Grade 1.
  • Active or inactive autoimmune disease or syndrome.
  • Active infection requiring systemic therapy.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful.
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Prior receipt of an IDO inhibitor.
  • Subjects with uncontrolled type I or type II diabetes mellitus (defined as HgbA1c > 8).
  • Prior receipt of a BET inhibitor (Treatment Group B only).
  • Subjects with a history of bleeding related to cancer under study requiring a medical intervention (eg, embolization procedure, RBC transfusion, or hospitalization) within 30 days of study enrollment (Treatment Groups B and C only).
  • Clinically significant bleeding within 14 days of Cycle 1 Day 1 (Treatment Groups B and C only).
  • Prior receipt of an LSD1 inhibitor including INCB059872 (Treatment Group C only).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02959437


Contacts
Contact: Incyte Corporation Call Center 1.855.463.3463 medinfo@incyte.com

Locations
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Principal Investigator: Fakih Marwan         
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Razelle Kurzrock         
United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Jason Luke         
United States, Pennsylvania
University of Pennsylvania Health System Recruiting
Philadelphia, Pennsylvania, United States, 19014
Principal Investigator: Peter Odwyer         
United States, Tennessee
Sarah Cannon Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Johanna Bendell         
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Laura Goff         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Naing Aung         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Elena Chiorean         
Spain
Vall D Hebron Univ Recruiting
Barcelona, Spain, 08035
Principal Investigator: Irene Brana         
Univ De Navarra Recruiting
Pamplona, Spain, 31008
Principal Investigator: Dr. Ignacio Melero         
United Kingdom
University College London Hospitals (Uclh) Recruiting
London, United Kingdom, W1t7ha
Principal Investigator: Rebecca Kristeleit         
Churchill Hospital Recruiting
Oxford, United Kingdom, Ox37le
Principal Investigator: Sarah Blagden         
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Kevin O'Hayer, MD Incyte Corporation

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02959437     History of Changes
Other Study ID Numbers: INCB 24360-206 / ECHO-206
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:
Solid tumors
NSCLC
CRC

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Pembrolizumab
Azacitidine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors