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

Solid Tumor Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03085914
• Other study ID #: INCB 24360-207 / ECHO-207
• Secondary ID: 2016-004678-16
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2, 2017
• Est. completion date: July 13, 2020

Study information

• Verified date: September 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: July 13, 2020
• Est. primary completion date: January 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Epacadostat
Epacadostat oral twice-daily continuous daily dosing at the protocol-defined dose.
• Pembrolizumab
Pembrolizumab
• Oxaliplatin
Oxaliplatin
• Leucovorin
Leucovorin
• 5-Fluorouracil
5-Fluorouracil
• Gemcitabine
Gemcitabine
• nab-Paclitaxel
nab-Paclitaxel
• Carboplatin
Carboplatin
• Paclitaxel
Paclitaxel
• Pemetrexed
Pemetrexed
• Cyclophosphamide
Cyclophosphamide
• Carboplatin
Carboplatin
• Cisplatin
Cisplatin
• 5-Fluorouracil
5-FU
• Investigator's choice of platinum agent
Investigator's choice of platinum agent: carboplatin or cisplatin

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Carolina Bio-Oncology Institute, PLLC	Huntersville	North Carolina
United States	Mayo Clinic	Jacksonville	Florida
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	Tennessee Oncology - Nashville; The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University; Henry Joyce Cancer Clinic	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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