A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)
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)
2 other identifiers
interventional
70
1 country
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2017
Typical duration for phase_1
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2017
CompletedFirst Posted
Study publicly available on registry
March 21, 2017
CompletedStudy Start
First participant enrolled
May 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 25, 2019
CompletedResults Posted
Study results publicly available
May 7, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 13, 2020
CompletedSeptember 23, 2022
September 1, 2022
1.7 years
February 28, 2017
January 21, 2020
September 12, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Up to 21 months
Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
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.
28 days
Phases 1 and 2: Objective Response Rate (ORR)
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.
Up to Week 18
Study Arms (7)
Treatment Group A
EXPERIMENTALEpacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)
Treatment Group B
EXPERIMENTALEpacadostat + pembrolizumab + gemcitabine and nab-paclitaxel
Treatment Group C
EXPERIMENTALEpacadostat + pembrolizumab + carboplatin and paclitaxel
Treatment Group D
EXPERIMENTALEpacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent
Treatment Group E
EXPERIMENTALEpacadostat + pembrolizumab + cyclophosphamide
Treatment Group F
EXPERIMENTALEpacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent
Treatment Group G
EXPERIMENTALEpacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil
Interventions
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
Pembrolizumab
Investigator's choice of platinum agent: carboplatin or cisplatin
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
University of California San Diego Medical Center, Moores Cancer Center
La Jolla, California, 92093, United States
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
Mayo Clinic
Jacksonville, Florida, 32224, United States
University of Chicago
Chicago, Illinois, 60637, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Carolina Bio-Oncology Institute, PLLC
Huntersville, North Carolina, 28078, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15237, United States
Tennessee Oncology - Nashville; The Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Vanderbilt University; Henry Joyce Cancer Clinic
Nashville, Tennessee, 37232, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112, United States
Related Publications (1)
Powderly JD, Klempner SJ, Naing A, Bendell J, Garrido-Laguna I, Catenacci DVT, Taylor MH, Lee JJ, Zheng F, Zhou F, Gong X, Gowda H, Beatty GL. Epacadostat Plus Pembrolizumab and Chemotherapy for Advanced Solid Tumors: Results from the Phase I/II ECHO-207/KEYNOTE-723 Study. Oncologist. 2022 Nov 3;27(11):905-e848. doi: 10.1093/oncolo/oyac174.
PMID: 36156099DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Enrollment in this study was permanently discontinued on 25 Oct 2018 due to a strategic decision and not based on safety concerns.
Results Point of Contact
- Title
- Study Director
- Organization
- Incyte Corporation
Study Officials
- STUDY DIRECTOR
Fred Zheng, MD
Incyte Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2017
First Posted
March 21, 2017
Study Start
May 2, 2017
Primary Completion
January 25, 2019
Study Completion
July 13, 2020
Last Updated
September 23, 2022
Results First Posted
May 7, 2020
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
- Access Criteria
- Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement
Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency