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

NCT03085914

Description:

This is an open-label, nonrandomized, Phase 1/2 study in subjects with advanced or metastatic solid tumors. Phase 1 is an assessment to evaluate the safety and tolerability of epacadostat when given in combination with pembrolizumab and chemotherapy. Once the recommended doses have been confirmed, subjects with advanced or metastatic CRC, PDAC, NSCLC (squamous or nonsquamous), UC, SCCHN or any advanced or metastatic solid tumor who progressed on previous therapy with a PD-1 or PD-L1 inhibitor will be enrolled in Phase 2.

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:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects 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: 24360-207 / ECHO-207
  • SECONDARY ID: 2016-004678-16
  • NCT ID: NCT03085914

Conditions

  • Advanced or Metastatic Solid Tumors
  • Advanced or Metastatic Colorectal Cancer (CRC)
  • Pancreatic Ductal Adenocarcinoma (PDAC)
  • Non-Small Cell Lung Cancer (NSCLC; Squamous or Nonsquamous)
  • Advanced or Metastatic Solid Tumor That Progressed on Previous Therapy With a Programmed Cell Death Protein 1 (PD-1) Inhibitor
  • Advanced or Metastatic Solid Tumor That Progressed on Previous Therapy With a Programmed Cell Death Ligand 1 (PD-L1) Inhibitor
  • Advanced or Metastatic Urothelial Carcinoma (UC)
  • Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

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

Purpose

This is an open-label, nonrandomized, Phase 1/2 study in subjects with advanced or metastatic solid tumors. Phase 1 is an assessment to evaluate the safety and tolerability of epacadostat when given in combination with pembrolizumab and chemotherapy. Once the recommended doses have been confirmed, subjects with advanced or metastatic CRC, PDAC, NSCLC (squamous or nonsquamous), UC, SCCHN or any advanced or metastatic solid tumor who progressed on previous therapy with a PD-1 or PD-L1 inhibitor will be enrolled in Phase 2.

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
Treatment Group EExperimentalEpacadostat + pembrolizumab + cyclophosphamide
  • Epacadostat
  • Pembrolizumab
  • Cyclophosphamide
  • Cisplatin
Treatment Group FExperimentalEpacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent
  • Epacadostat
  • Pembrolizumab
  • Gemcitabine
  • Carboplatin
  • Cisplatin
Treatment Group GExperimentalEpacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil
  • Epacadostat
  • Pembrolizumab
  • 5-Fluorouracil
  • Carboplatin
  • Cisplatin

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:Phase 1: Safety and tolerability assessed by frequency, duration, and severity of adverse events (AEs)
Time Frame:Through 90 days after end of treatment, estimated to be up to 27 months per subject
Safety Issue:
Description:A treatment-emergent AE is defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE is defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE is graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).

Secondary Outcome Measures

Measure:Phase 1: ORR based on RECIST v1.1
Time Frame:Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject
Safety Issue:
Description:Defined as percentage of subjects with a CR or PR
Measure:Phase 2: Safety and tolerability assessed by frequency, duration, and severity of AEs
Time Frame:Through 90 days after end of treatment, estimated to be up to 27 months per subject
Safety Issue:
Description:A treatment-emergent AE is defined as an event occurring after exposure to at least 1 dose of study drug. A treatment-related AE is defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE is graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).
Measure:Phases 1 and 2: Duration of response (DOR) per RECIST v1.1
Time Frame:Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject
Safety Issue:
Description:DOR defined as time from earliest date of CR or PR until the earliest date of disease progression or death due to any cause, if occurring sooner than disease progression.
Measure:Phases 1 and 2: Progression-free survival RECIST v1.1
Time Frame:Every 9 weeks through duration of treatment, estimated to be up to 24 months per subject
Safety Issue:
Description:Defined as time from date of first dose of study medication until the earliest date of disease progression or death due to any cause, if occurring sooner than progression.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
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

December 14, 2017