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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03085914
Recruitment Status : Active, not recruiting
First Posted : March 21, 2017
Results First Posted : February 17, 2020
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:

This was an open-label, nonrandomized, Phase 1/2 study designed to determine the safety, tolerability, and efficacy of epacadostat when given in combination with pembrolizumab and 7 different chemotherapy regimens described as Treatment Groups A through G below (see Study Drug and Background Therapies, Dose, and Mode of Administration). Phase 1 consisted of a 3 + 3 + 3 design intended to determine the MTD or PAD of epacadostat when given in combination with pembrolizumab and chemotherapy; efficacy was also explored.

Phase 2 was designed to enroll efficacy expansion cohorts to further evaluate the safety, tolerability, and efficacy of epacadostat at the MTD or PAD (as selected in Phase 1) when given in combination with pembrolizumab and chemotherapy. Each efficacy expansion cohort was to enroll participants with 1 specific type of advanced or metastatic solid tumor. Additional cohorts (ie, the mandatory biopsy cohorts) were designed to evaluate changes in the tumor microenvironment in participants with any advanced or metastatic solid tumor who had progressed on previous therapy with a PD-1 or a PD-L1 inhibitor.

No participants were enrolled in any Phase 2 efficacy expansion cohort, or in any Phase 2 mandatory biopsy cohort receiving Treatment A, B, F, or G. Phase 2 mandatory biopsy cohort participants received Treatments C, D, or E (ie, were included in Treatment Groups C, D, or E). Participants were assigned to a treatment group based on the chemotherapy regimen most appropriate for their tumor type.


Condition or disease Intervention/treatment Phase
Solid Tumor 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 Drug: Investigator's choice of platinum agent Phase 1 Phase 2

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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
Actual Primary Completion Date : January 25, 2019
Estimated Study Completion Date : November 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

Drug: Oxaliplatin
Oxaliplatin

Drug: Leucovorin
Leucovorin

Drug: 5-Fluorouracil
5-Fluorouracil

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

Drug: Gemcitabine
Gemcitabine

Drug: nab-Paclitaxel
nab-Paclitaxel

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

Drug: Carboplatin
Carboplatin

Drug: Paclitaxel
Paclitaxel

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

Drug: Pemetrexed
Pemetrexed

Drug: Carboplatin
Carboplatin

Drug: Cisplatin
Cisplatin

Drug: Investigator's choice of platinum agent
Investigator's choice of platinum agent: carboplatin or cisplatin

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

Drug: Cyclophosphamide
Cyclophosphamide

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

Drug: Gemcitabine
Gemcitabine

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

Drug: Carboplatin
Carboplatin

Drug: Cisplatin
Cisplatin

Drug: 5-Fluorouracil
5-FU

Drug: Investigator's choice of platinum agent
Investigator's choice of platinum agent: carboplatin or cisplatin




Primary Outcome Measures :
  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From study start up to clinical data cut-off date of 25 Jan 2019 (approximately 21 months) ]
    A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.

  2. Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: 28 days ]
    A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.

  3. Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to Week 18 ]
    ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.


Secondary Outcome Measures :
  1. Phase 1: Objective Response Rate (ORR) [ Time Frame: Up to Week 18 ]
    ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  2. Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAE [ Time Frame: Through 90 days after end of treatment, estimated to be up to a minimum of 18 weeks per participant ]
    A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect, is a medically important event that may jeopardize an event that may jeopardize the subject or may require medical or surgical intervention to prevent 1 of the outcomes listed above.



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.


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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
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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
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Study Director: Fred Zheng, MD Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] February 14, 2019
Statistical Analysis Plan  [PDF] March 12, 2019

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03085914    
Other Study ID Numbers: INCB 24360-207 / ECHO-207
2016-004678-16 ( EudraCT Number )
First Posted: March 21, 2017    Key Record Dates
Results First Posted: February 17, 2020
Last Update Posted: May 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Neoplasms
Leucovorin
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Fluorouracil
Oxaliplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Antineoplastic Agents, Immunological