Clinical Trials /

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

NCT03085914

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Urothelial Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT03085914

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: INCB 24360-207 / ECHO-207
  • SECONDARY ID: 2016-004678-16
  • NCT ID: NCT03085914

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
EpacadostatINCB024360Treatment Group A
PembrolizumabTreatment Group A
OxaliplatinTreatment Group A
LeucovorinTreatment Group A
5-FluorouracilTreatment Group A
GemcitabineTreatment Group B
nab-PaclitaxelTreatment Group B
CarboplatinTreatment Group C
PaclitaxelTreatment Group C
PemetrexedTreatment Group D
CyclophosphamideTreatment Group E
CarboplatinTreatment Group D
CisplatinTreatment Group D
5-FluorouracilTreatment Group G
Investigator's choice of platinum agentTreatment Group D

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Treatment Group AExperimentalEpacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)
  • Epacadostat
  • Pembrolizumab
  • Oxaliplatin
  • Leucovorin
  • 5-Fluorouracil
Treatment Group BExperimentalEpacadostat + pembrolizumab + gemcitabine and nab-paclitaxel
  • Epacadostat
  • Pembrolizumab
  • Gemcitabine
  • nab-Paclitaxel
Treatment Group CExperimentalEpacadostat + pembrolizumab + carboplatin and paclitaxel
  • Epacadostat
  • Pembrolizumab
  • Carboplatin
  • Paclitaxel
Treatment Group DExperimentalEpacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent
  • Epacadostat
  • Pembrolizumab
  • Pemetrexed
  • Carboplatin
  • Cisplatin
  • Investigator's choice of platinum agent
Treatment Group EExperimentalEpacadostat + pembrolizumab + cyclophosphamide
  • Epacadostat
  • Pembrolizumab
  • Cyclophosphamide
Treatment Group FExperimentalEpacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent
  • Epacadostat
  • Pembrolizumab
  • Gemcitabine
Treatment Group GExperimentalEpacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil
  • Epacadostat
  • Pembrolizumab
  • Carboplatin
  • Cisplatin
  • 5-Fluorouracil
  • Investigator's choice of platinum agent

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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time Frame:Up to 21 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Incyte Corporation

Trial Keywords

  • solid tumors
  • colorectal cancer
  • pancreatic ductal adenocarcinoma
  • non-small cell lung cancer
  • PD-1
  • PD-L1
  • epacadostat
  • IDO inhibitor

Last Updated

August 5, 2021