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A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)

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ClinicalTrials.gov Identifier: NCT03085914
Recruitment Status : Active, not recruiting
First Posted : March 21, 2017
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
This is an open-label, nonrandomized, Phase 1/2 study in subjects with advanced or metastatic solid tumors. Phase 1 is an assessment to evaluate the safety and tolerability of epacadostat when given in combination with pembrolizumab and chemotherapy. Once the recommended doses have been confirmed, subjects with advanced or metastatic CRC, PDAC, NSCLC (squamous or nonsquamous), UC, SCCHN or any advanced or metastatic solid tumor who progressed on previous therapy with a PD-1 or PD-L1 inhibitor will be enrolled in Phase 2.

Condition or disease Intervention/treatment Phase
Solid Tumors Colorectal Cancer (CRC) Adenocarcinoma (PDAC) Lung Cancer UC (Urothelial Cancer) Head and Neck Cancer Drug: Epacadostat Drug: Pembrolizumab Drug: Oxaliplatin Drug: Leucovorin Drug: 5-Fluorouracil Drug: Gemcitabine Drug: nab-Paclitaxel Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed Drug: Cyclophosphamide Drug: Cisplatin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)
Actual Study Start Date : May 2, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Group A
Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Oxaliplatin
Oxaliplatin 85 mg/m^2 IV on Days 1 and 15

Drug: Leucovorin
Leucovorin 400 mg/m^2 IV on Days 1 and 15

Drug: 5-Fluorouracil
5-Fluorouracil total dose of 2400 mg/m^2 on Days 1 and 15

Experimental: Treatment Group B
Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15

Drug: nab-Paclitaxel
nab-Paclitaxel 125 mg/m^2 IV on Days 1, 8, and 15

Experimental: Treatment Group C
Epacadostat + pembrolizumab + carboplatin and paclitaxel
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Carboplatin
Carboplatin AUC 6 IV on Day 1 every 3 weeks

Drug: Paclitaxel
Paclitaxel 200 mg/m^2 IV on Day 1 every 3 weeks

Experimental: Treatment Group D
Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Pemetrexed
Pemetrexed 500 mg/m^2 IV on Day 1 every 3 weeks

Drug: Carboplatin
Carboplatin AUC 5 IV on Day 1 every 3 weeks

Drug: Cisplatin
Cisplatin 75 mg/m^2 on Day 1 every 3 weeks

Experimental: Treatment Group E
Epacadostat + pembrolizumab + cyclophosphamide
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Cyclophosphamide
Cyclophosphamide 50 mg orally once daily

Drug: Cisplatin
Cisplatin 75 mg/m^2 on Day 1 every 3 weeks

Experimental: Treatment Group F
Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15

Drug: Carboplatin
Carboplatin AUC 6 IV on Day 1 every 3 weeks

Drug: Cisplatin
Cisplatin 75 mg/m^2 on Day 1 every 3 weeks

Experimental: Treatment Group G
Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil
Drug: Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose
Other Name: INCB024360

Drug: Pembrolizumab
Pembrolizumab 200 mg IV every 3 weeks

Drug: 5-Fluorouracil
5-Fluorouracil total dose of 2400 mg/m^2 on Days 1 and 15

Drug: Carboplatin
Carboplatin AUC 6 IV on Day 1 every 3 weeks

Drug: Cisplatin
Cisplatin 75 mg/m^2 on Day 1 every 3 weeks




Primary Outcome Measures :
  1. Phase 1: Safety and tolerability assessed by frequency, duration, and severity of adverse events (AEs) [ Time Frame: Through 90 days after end of treatment, estimated to be up to 27 months per subject ]
    A treatment-emergent AE is defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE is 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 is 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. Phase 2: Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) [ Time Frame: Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject ]
    Defined as percentage of subjects with a complete response (CR) or partial response (PR)


Secondary Outcome Measures :
  1. Phase 1: ORR based on RECIST v1.1 [ Time Frame: Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject ]
    Defined as percentage of subjects with a CR or PR

  2. Phase 2: Safety and tolerability assessed by frequency, duration, and severity of AEs [ Time Frame: Through 90 days after end of treatment, estimated to be up to 27 months per subject ]
    A treatment-emergent AE is defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE is 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 is 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. Phases 1 and 2: Duration of response (DOR) per RECIST v1.1 [ Time Frame: Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject ]
    DOR defined as time from earliest date of CR or PR until the earliest date of disease progression or death due to any cause, if occurring sooner than disease progression.

  4. Phases 1 and 2: Progression-free survival RECIST v1.1 [ Time Frame: Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject ]
    Defined as time from date of first dose of study medication until the earliest date of disease progression or death due to any cause, if occurring sooner than progression.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
  • Presence of measurable disease per RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

  • Laboratory and medical history parameters not within the Protocol-defined range.
  • Receipt of anticancer medications or investigational drugs within the Protocol-defined intervals before the first administration of study drug.
  • Previous radiotherapy within 2 weeks of starting study therapy.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy.
  • Receipt of a live vaccine within 30 days of planned start of study therapy.
  • Active infection requiring systemic therapy.
  • Subjects who have any active or inactive autoimmune disease or syndrome.
  • Women who are pregnant or breastfeeding.

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): NCT03085914


Locations
United States, Arizona
Mayo Clinic Arizona
Phoenix, Arizona, United States, 85054
United States, California
University of California San Diego Medical Center, Moores Cancer Center
La Jolla, California, United States, 92093
The Angeles Clinic and Research Institute
Los Angeles, California, United States, 90025
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Carolina Bio-Oncology Institute, PLLC
Huntersville, North Carolina, United States, 28078
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15237
United States, Tennessee
Tennessee Oncology - Nashville; The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Vanderbilt University; Henry Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Fred Zheng, MD Incyte Corporation

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03085914     History of Changes
Other Study ID Numbers: 24360-207 / ECHO-207
2016-004678-16 ( EudraCT Number )
First Posted: March 21, 2017    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 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
colorectal cancer
pancreatic ductal adenocarcinoma
non-small cell lung cancer
PD-1
PD-L1
epacadostat
IDO inhibitor

Additional relevant MeSH terms:
Colorectal Neoplasms
Adenocarcinoma
Head and Neck Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Gemcitabine
Oxaliplatin
Pembrolizumab
Albumin-Bound Paclitaxel
Cisplatin
Cyclophosphamide
Carboplatin
Fluorouracil
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents