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

NCT ID: NCT03085914

Last Updated: 2022-09-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-02

Study Completion Date

2020-07-13

Brief Summary

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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.

Detailed Description

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Conditions

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Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment Group A

Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Oxaliplatin

Intervention Type DRUG

Oxaliplatin

Leucovorin

Intervention Type DRUG

Leucovorin

5-Fluorouracil

Intervention Type DRUG

5-Fluorouracil

Treatment Group B

Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Gemcitabine

Intervention Type DRUG

Gemcitabine

nab-Paclitaxel

Intervention Type DRUG

nab-Paclitaxel

Treatment Group C

Epacadostat + pembrolizumab + carboplatin and paclitaxel

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Carboplatin

Intervention Type DRUG

Carboplatin

Paclitaxel

Intervention Type DRUG

Paclitaxel

Treatment Group D

Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Pemetrexed

Intervention Type DRUG

Pemetrexed

Carboplatin

Intervention Type DRUG

Carboplatin

Cisplatin

Intervention Type DRUG

Cisplatin

Investigator's choice of platinum agent

Intervention Type DRUG

Investigator's choice of platinum agent: carboplatin or cisplatin

Treatment Group E

Epacadostat + pembrolizumab + cyclophosphamide

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide

Treatment Group F

Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Gemcitabine

Intervention Type DRUG

Gemcitabine

Treatment Group G

Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil

Group Type EXPERIMENTAL

Epacadostat

Intervention Type DRUG

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Pembrolizumab

Intervention Type DRUG

Pembrolizumab

Carboplatin

Intervention Type DRUG

Carboplatin

Cisplatin

Intervention Type DRUG

Cisplatin

5-Fluorouracil

Intervention Type DRUG

5-FU

Investigator's choice of platinum agent

Intervention Type DRUG

Investigator's choice of platinum agent: carboplatin or cisplatin

Interventions

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Epacadostat

Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.

Intervention Type DRUG

Pembrolizumab

Pembrolizumab

Intervention Type DRUG

Oxaliplatin

Oxaliplatin

Intervention Type DRUG

Leucovorin

Leucovorin

Intervention Type DRUG

5-Fluorouracil

5-Fluorouracil

Intervention Type DRUG

Gemcitabine

Gemcitabine

Intervention Type DRUG

nab-Paclitaxel

nab-Paclitaxel

Intervention Type DRUG

Carboplatin

Carboplatin

Intervention Type DRUG

Paclitaxel

Paclitaxel

Intervention Type DRUG

Pemetrexed

Pemetrexed

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide

Intervention Type DRUG

Carboplatin

Carboplatin

Intervention Type DRUG

Cisplatin

Cisplatin

Intervention Type DRUG

5-Fluorouracil

5-FU

Intervention Type DRUG

Investigator's choice of platinum agent

Investigator's choice of platinum agent: carboplatin or cisplatin

Intervention Type DRUG

Other Intervention Names

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INCB024360

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fred Zheng, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

University of California San Diego Medical Center, Moores Cancer Center

La Jolla, California, United States

Site Status

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Carolina Bio-Oncology Institute, PLLC

Huntersville, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology - Nashville; The Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt University; Henry Joyce Cancer Clinic

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 36156099 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-004678-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 24360-207 / ECHO-207

Identifier Type: -

Identifier Source: org_study_id

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