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A Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02327078
Recruitment Status : Completed
First Posted : December 30, 2014
Results First Posted : April 26, 2023
Last Update Posted : April 26, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Incyte Corporation

Study Description
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Brief Summary:

This is a Phase 1/2, open label study. Phase 1 consists of 2 parts. Part 1 is a dose-escalation assessment of the safety and tolerability of epacadostat administered with nivolumab in subjects with select advanced solid tumors and lymphomas. Part 2 will evaluate the safety and tolerability of epacadostat in combination with nivolumab and chemotherapy in subjects with squamous cell carcinoma of head and neck (SCCHN) and non-small cell lung cancer (NSCLC).

Phase 2 will include expansion cohorts in 7 tumor types, including melanoma, NSCLC, SCCHN, colorectal cancer, ovarian cancer, glioblastoma and diffuse large B-cell lymphoma (DLBCL).


Condition or disease Intervention/treatment Phase
B-cell Malignancies Colorectal Cancer (CRC) Head and Neck Cancer Lung Cancer Lymphoma Melanoma Ovarian Cancer Glioblastoma Drug: Nivolumab Drug: Epacadostat Drug: Chemotherapy Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 307 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204)
Actual Study Start Date : November 26, 2014
Actual Primary Completion Date : June 16, 2020
Actual Study Completion Date : June 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab
Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose
Experimental: Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab
Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose
Experimental: Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose
Experimental: Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose
Experimental: Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360mg Q3W and 5-FU/Platinum( Carboplatin or Cisplatin+5-Fluorouracil) administered intravenously (IV).
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose

Drug: Chemotherapy
Specified dose on specified days
Experimental: Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Pemetrexed/Platinum (Carboplatin orCisplatin+Pemetrexed) administered intravenously (IV).
 Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose

Drug: Chemotherapy
Specified dose on specified days
Experimental: Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Paclitaxel/Platinum(Carboplatin+Cisplatin+Paclitaxel)administered intravenously (IV).
 Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose

Drug: Chemotherapy
Specified dose on specified days
Experimental: Phase 2 Epacadostat 100mg BID + Nivolumab
Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W or 480 mg Q4W based on tumor type administered intravenously (IV).
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose
Experimental: Phase 2 Epacadostat 300mg BID + Nivolumab
Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV).
 Drug: Nivolumab
specified dose and dosing schedule

Drug: Epacadostat
oral twice daily continuous at the protocol-defined dose


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 42 ]
    A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT > 3 × upper limit of normal (ULN) and concurrent total bilirubin > 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.

  2. Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 42 ]
    A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT > 3 × upper limit of normal (ULN) and concurrent total bilirubin > 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.

  3. Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) [ Time Frame: up to approximately 39 months ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.

  4. Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    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 RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.

  5. Phase 2: Progression Free Survival (PFS) [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first.

  6. Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma [ Time Frame: Month 9 ]
    OS rate is defined as the proportion of participants alive 9 months after the start of treatment.


Secondary Outcome Measures :
  1. Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters.

  2. Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Per Cheson criteria, CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses. Per RANO criteria, CR: Complete disappearance of all enhancing measurable and non-measurable disease sustained. PR: at least ≥50% decrease compared with baseline in the SOD of all measurable enhancing lesions sustained.

  3. Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.

  4. Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first.

  5. Phase 2: Duration of Response [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.

  6. Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) [ Time Frame: From first dose up end of the study (up to approximately 6 years) ]
    Duration of disease control is the time from the first dose to the first objective response of PD, or death, whichever occurs first, for participants who reported a best overall response of SD or better. PD was defined as at least a 20% increase in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters.

  7. Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs [ Time Frame: up to approximately 35 months ]
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. Adverse events of grade 5 which result in death are called as fatal AEs.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects, age 18 years or older
  • Subjects with histologically or cytologically confirmed NSCLC, MEL (including I/O relapsed MEL or I/O refractory MEL), CRC, SCCHN, ovarian cancer, recurrent B cell NHL or HL, or glioblastoma
  • Presence of measurable disease by RECIST v1.1 for solid tumors or Cheson criteria for B cell NHL (including DLBCL) or HL. For subjects with glioblastoma, presence of measurable disease is not required.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Fresh baseline tumor biopsies (defined as a biopsy specimen taken since completion of the most recent prior chemotherapy regimen) are required for all cohorts except glioblastoma

Exclusion Criteria:

  • Laboratory and medical history parameters not within Protocol-defined range
  • Currently pregnant or breastfeeding
  • Subjects who have received prior immune checkpoint inhibitors or an IDO inhibitor (except select Phase 2 cohorts evaluating I/O relapsed or I/O refractory MEL). Subjects who have received experimental vaccines or other immune therapies should be discussed with the medical monitor to confirm eligibility
  • Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
  • Subjects with any active or inactive autoimmune process
  • Evidence of interstitial lung disease or active, noninfectious pneumonitis
  • Subjects with any active or inactive autoimmune process
  • Ocular MEL
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02327078


Locations
Show Show 24 study locations
Sponsors and Collaborators
Incyte Corporation
Bristol-Myers Squibb
Investigators
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Study Director: Lance Leopold Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] May 31, 2018
Statistical Analysis Plan  [PDF] March 5, 2019

More Information
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02327078    
Other Study ID Numbers: INCB 24360-204 / ECHO-204
First Posted: December 30, 2014    Key Record Dates
Results First Posted: April 26, 2023
Last Update Posted: April 26, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Astrocytoma
Glioma
 Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action