Clinical trial NCT03085914: A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: solid tumors
colorectal cancer
pancreatic ductal adenocarcinoma
non-small cell lung cancer
PD-1
PD-L1
epacadostat
IDO inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-03-21
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Up to 21 months
measure: Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: 28 days
measure: Phases 1 and 2: Objective Response Rate (ORR)
timeFrame: Up to Week 18
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego Medical Center, Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina Bio-Oncology Institute, PLLC
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville; The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University; Henry Joyce Cancer Clinic
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
Study officials:
affiliation: Incyte Corporation
name: Fred Zheng, MD
role: STUDY_DIRECTOR
References:
citation: 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.