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

NCT02327078 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: INCB 24360-204 / ECHO-2042016-002423-29
• Study Type: interventional
• Target: 307
• Locations: 2 countries
• Sites: 24

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).

Conditions

B-cell Malignancies; Colorectal Cancer (CRC); Head and Neck Cancer; Lung Cancer; Lymphoma; Melanoma; Ovarian Cancer; Glioblastoma

Outcome Measures

Primary Outcomes (6)

• Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)

  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.

  Day 42

• Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)

  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.

  Day 42

• Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)

  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.

  up to approximately 39 months

• 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

  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.

  From first dose up end of the study (up to approximately 6 years)

• Phase 2: Progression Free Survival (PFS)

  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.

  From first dose up end of the study (up to approximately 6 years)

• Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma

  OS rate is defined as the proportion of participants alive 9 months after the start of treatment.

  Month 9

Secondary Outcomes (7)

• Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC

  From first dose up end of the study (up to approximately 6 years)

• 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

  From first dose up end of the study (up to approximately 6 years)

• Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC

  From first dose up end of the study (up to approximately 6 years)

• Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC

  From first dose up end of the study (up to approximately 6 years)

• Phase 2: Duration of Response

  From first dose up end of the study (up to approximately 6 years)

Study Arms (9)

Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab

EXPERIMENTAL

Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W

Drug: Nivolumab; Drug: Epacadostat

Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab

EXPERIMENTAL

Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W

Drug: Nivolumab; Drug: Epacadostat

Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab

EXPERIMENTAL

Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.

Drug: Nivolumab; Drug: Epacadostat

Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab

EXPERIMENTAL

Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W.

Drug: Nivolumab; Drug: Epacadostat

Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum

EXPERIMENTAL

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; Drug: Epacadostat; Drug: Chemotherapy

Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum

EXPERIMENTAL

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; Drug: Chemotherapy

Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum

EXPERIMENTAL

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; Drug: Chemotherapy

Phase 2 Epacadostat 100mg BID + Nivolumab

EXPERIMENTAL

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; Drug: Epacadostat

Phase 2 Epacadostat 300mg BID + Nivolumab

EXPERIMENTAL

Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV).

Drug: Nivolumab; Drug: Epacadostat

Interventions

Nivolumab DRUG

specified dose and dosing schedule

Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab; Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum; Phase 2 Epacadostat 100mg BID + Nivolumab; Phase 2 Epacadostat 300mg BID + Nivolumab

Epacadostat DRUG

oral twice daily continuous at the protocol-defined dose

Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab; Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab; Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum; Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum; Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum; Phase 2 Epacadostat 100mg BID + Nivolumab; Phase 2 Epacadostat 300mg BID + Nivolumab

Chemotherapy DRUG

Specified dose on specified days

Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum; Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum; Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead
• Bristol-Myers Squibb: collaborator

Study Sites (24)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

UCSF - University of California San Francisco

San Francisco, California, 94115, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

The University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

NYU Cancer Center

New York, New York, 10016, United States

Location

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Medical Center Boulevard

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Research

Fargo, North Dakota, 58122, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15232, United States

Location

Sanford Research

North Sioux City, South Dakota, 57104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology Research

Austin, Texas, 78705, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Lymphoma; Melanoma; Ovarian Neoplasms; Glioblastoma

Interventions

Nivolumab; epacadostat; Drug Therapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Lance Leopold

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2014
• First Posted: December 30, 2014
• Study Start: November 26, 2014
• Primary Completion: June 16, 2020
• Study Completion: June 16, 2020
• Last Updated: August 14, 2025
• Results First Posted: April 26, 2023

Record last verified: 2025-08

Locations

US (22); GB (2)