Clinical Trials /

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

NCT02959437

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: INCB 24360-206 / ECHO-206
  • NCT ID: NCT02959437

Conditions

  • Solid Tumor
  • Advanced Cancer
  • Metastatic Cancer

Interventions

DrugSynonymsArms
AzacitidineAzacitidine + Pembrolizumab + Epacadostat
PembrolizumabAzacitidine + Pembrolizumab + Epacadostat
EpacadostatAzacitidine + Pembrolizumab + Epacadostat

Purpose

This is an open-label, Phase 1/2 study in subjects with advanced or metastatic solid tumors. 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 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. Once the recommended doses have been determined, subjects with previously treated NSCLC and microsatellite-stable colorectal cancer (CRC) will be enrolled into expansion cohorts in Part 2.

Trial Arms

NameTypeDescriptionInterventions
Azacitidine + Pembrolizumab + EpacadostatExperimentalPart 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.
  • Azacitidine
  • Pembrolizumab
  • Epacadostat

Eligibility Criteria

        Inclusion Criteria:

          -  Willingness to provide written informed consent for the study.

          -  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: Subjects with histologically or cytologically confirmed NSCLC:

               -  Stage IIIB or metastatic (Stage IV) 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 (except Cohort
                  A1, which must be checkpoint inhibitor-naive).

               -  Must have disease progression on a prior PD-1-pathway targeted agent (Cohort A2)
                  or must be PD-1 pathway-targeted treatment naive (Cohort A1).

          -  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 KRAS wild type and no contraindication,
                  an anti-epidermal growth factor receptor (EGFR) therapy; and progressed after the
                  last administration of approved therapy.

          -  Has baseline tumor biopsy specimen available or willingness to undergo a pretreatment
             and on-treatment tumor biopsy to obtain the specimen.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Part 1: Objective response rate based on mRECIST v1.1
Time Frame:Every 9 weeks for the duration of study participation; estimated to be 18 months
Safety Issue:
Description:Defined as the percentage of subjects having a complete response or partial response.
Measure: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.
Safety Issue:
Description: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).
Measure:Parts 1 and 2: Percentage of responders determined by immunohistochemistry
Time Frame:Baseline and Week 5 or Week 6.
Safety Issue:
Description: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.
Measure:Parts 1 and 2: Progression-free survival based on mRECIST v1.1.
Time Frame:Every 9 weeks for the duration of study participation; estimated to be 18 months.
Safety Issue:
Description:Defined as the time from date of first dose of study drug until the earliest date of disease progression per mRECIST v1.1, or death due to any cause, if occurring sooner than progression.
Measure:Parts 1 and 2: Duration of response based on mRECIST v1.1
Time Frame:Every 9 weeks for the duration of study participation; estimated to be 18 months.
Safety Issue:
Description:Defined as the time from earliest date of disease response until the earliest date of disease progression per mRECIST v1.1, or death due to any cause, if occurring sooner than progression.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Solid tumors
  • NSCLC
  • CRC

Last Updated

January 10, 2018