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

Incyte Corporation70 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor

Interventions

EpacadostatDRUG

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

PembrolizumabDRUG

Pembrolizumab

OxaliplatinDRUG

Oxaliplatin

LeucovorinDRUG

Leucovorin

5-FluorouracilDRUG

5-Fluorouracil

GemcitabineDRUG

Gemcitabine

nab-PaclitaxelDRUG

nab-Paclitaxel

CarboplatinDRUG

Carboplatin

PaclitaxelDRUG

Paclitaxel

PemetrexedDRUG

Pemetrexed

CyclophosphamideDRUG

Cyclophosphamide

CarboplatinDRUG

Carboplatin

CisplatinDRUG

Cisplatin

5-FluorouracilDRUG

5-FU

Investigator's choice of platinum agentDRUG

Investigator's choice of platinum agent: carboplatin or cisplatin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (16)

Mayo Clinic Arizona

Phoenix, Arizona, United States

University of California San Diego Medical Center, Moores Cancer Center

La Jolla, California, United States

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Mayo Clinic

Jacksonville, Florida, United States

University of Chicago

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Carolina Bio-Oncology Institute, PLLC

Huntersville, North Carolina, United States

Oregon Health and Science University

Portland, Oregon, United States

...and 6 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to Week 18