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)

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Gemcitabine; Drug: Carboplatin; Drug: Paclitaxel; Drug: 5-Fluorouracil; Drug: Epacadostat; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: nab-Paclitaxel; Drug: Pemetrexed; Drug: Investigator's choice of platinum agent

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Group A; Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)	Drug: Pembrolizumab; Pembrolizumab; Drug: 5-Fluorouracil; 5-FU; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360; Drug: Oxaliplatin; Oxaliplatin; Drug: Leucovorin; Leucovorin; Drug: 5-Fluorouracil; 5-Fluorouracil
EXPERIMENTAL: Treatment Group B; Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel	Drug: Pembrolizumab; Pembrolizumab; Drug: Gemcitabine; Gemcitabine; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360; Drug: nab-Paclitaxel; nab-Paclitaxel
EXPERIMENTAL: Treatment Group C; Epacadostat + pembrolizumab + carboplatin and paclitaxel	Drug: Pembrolizumab; Pembrolizumab; Drug: Carboplatin; Carboplatin; Drug: Paclitaxel; Paclitaxel; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360
EXPERIMENTAL: Treatment Group D; Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent	Drug: Pembrolizumab; Pembrolizumab; Drug: Cisplatin; Cisplatin; Drug: Carboplatin; Carboplatin; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360; Drug: Pemetrexed; Pemetrexed; Drug: Investigator's choice of platinum agent; Investigator's choice of platinum agent: carboplatin or cisplatin
EXPERIMENTAL: Treatment Group E; Epacadostat + pembrolizumab + cyclophosphamide	Drug: Cyclophosphamide; Cyclophosphamide; Drug: Pembrolizumab; Pembrolizumab; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360
EXPERIMENTAL: Treatment Group F; Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent	Drug: Pembrolizumab; Pembrolizumab; Drug: Gemcitabine; Gemcitabine; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360
EXPERIMENTAL: Treatment Group G; Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil	Drug: Pembrolizumab; Pembrolizumab; Drug: Cisplatin; Cisplatin; Drug: Carboplatin; Carboplatin; Drug: 5-Fluorouracil; 5-FU; Drug: Epacadostat; Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.; Other Names: INCB024360; Drug: 5-Fluorouracil; 5-Fluorouracil; Drug: Investigator's choice of platinum agent; Investigator's choice of platinum agent: carboplatin or cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Incyte Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 2, 2017
• Primary Completion (ACTUAL): January 25, 2019
• Study Completion (ACTUAL): July 13, 2020

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 20, 2017
• First Posted (ACTUAL): March 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: colorectal cancer; non-small cell lung cancer; PD-1; PD-L1; solid tumors; pancreatic ductal adenocarcinoma; epacadostat; IDO inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Folic Acid Antagonists; Gemcitabine; Cyclophosphamide; Carboplatin; Paclitaxel; Fluorouracil; Oxaliplatin; Pembrolizumab; Leucovorin; Albumin-Bound Paclitaxel; Pemetrexed
• Other Study ID Numbers: INCB 24360-207 / ECHO-207; 2016-004678-16 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No