A Study Of Epacadostat In Combination With Pembrolizumab And Chemotherapy In Participants With Advanced Or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)

Study Overview

A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants 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.

N/A

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: Carboplatin
DRUG: Cisplatin
DRUG: 5-Fluorouracil
DRUG: Investigator's choice of platinum agent

INCB 24360-207 / ECHO-207
2016-004678-16 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-02-28	Results First Submitted 2020-01-21	Last Update Submitted that met QC Criteria 2022-09-12
First Submitted that Met QC Criteria 2017-03-20	Results First Submitted that Met QC Criteria 2020-04-27	Last Update Posted (ACTUAL) 2022-09-23
First Posted (ACTUAL) 2017-03-21	Results First Posted 2020-05-07	Last Verified 2022-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/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. 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. 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. 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. 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. 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. 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. 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	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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Fred Zheng, MD, Incyte Corporation

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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.

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