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

• ClinicalTrials.gov Identifier: NCT02327078
• Recruitment Status: Completed
• First Posted: December 30, 2014
• Last Update Posted: August 28, 2020
• Sponsor: Incyte Corporation
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Incyte Corporation

Study Description

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 (Phase 1); Drug: Epacadostat (Phase 1); Drug: Chemotherapy (Phase 1); Drug: Nivolumab (Phase 2); Drug: Epacadostat (Phase 2)	Phase 1; Phase 2

Study Design

• 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: July 10, 2020
• Actual Study Completion Date: July 10, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: (Phase 1, Part 1) : Nivolumab + Epacadostat	Drug: Nivolumab (Phase 1); specified dose and dosing schedule; Drug: Epacadostat (Phase 1); oral twice daily continuous at the protocol-defined dose
Experimental: (Phase 2): Nivolumab + Epacadostat	Drug: Nivolumab (Phase 2); specified dose and dosing schedule; Drug: Epacadostat (Phase 2); oral twice daily continuous at the protocol-defined dose
Experimental: (Phase 1, Part 2): Nivolumab + Epacadostat + Chemotherapy	Drug: Nivolumab (Phase 1); specified dose and dosing schedule; Drug: Epacadostat (Phase 1); oral twice daily continuous at the protocol-defined dose; Drug: Chemotherapy (Phase 1); Specified dose on specified days

Outcome Measures

Primary Outcome Measures :

1. Phase 1, Part 1: Safety and tolerability of epacadostat and nivolumab assessed by number of subjects with dose limiting toxicities (DLTs) [ Time Frame: 42 days ]
   A DLT was defined as the occurrence of any of the toxicities occurring up to and including Day 42 in Phase 1 Parts 1 and 2.
2. Phase 1, Part 2: Safety and tolerability of epacadostat administered in combination with nivolumab and chemotherapy regimen assessed by number of subjects with DLTs [ Time Frame: 42 days ]
   A DLT was defined as the occurrence of any of the toxicities occurring up to and including Day 42 in Phase 1 Parts 1 and 2.
3. Phase 1, Part 1 and 2: Safety assessed by the frequency of adverse events, serious adverse events, and deaths [ Time Frame: From study start up to clinical data cut-off date of 01 Feb 2019 ]
   A treatment-emergent adverse event (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) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with solid tumors and per Cheson criteria for subjects with DLBCL [ Time Frame: Response is assessed every 8 weeks up to 6 months ]
   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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Cheson criteria for DLBCL and RANO criteria for Glioblastoma.
5. Phase 2: Progression free survival (PFS) [ Time Frame: Response is assessed every 8 weeks up to 6 months ]
   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) for subjects with Glioblatoma [ Time Frame: Subjects will be followed-up for survival every 12 weeks for a minimum of 9 months. ]
   Overall survival is defined as the time from the date of the first dose of study treatment to death due to any cause.

Secondary Outcome Measures :

1. Phase 1, Part 1: ORR per RECIST v1.1 and mRECIST for subjects with solid tumors; per Cheson and mCheson criteria for subjects with B-cell NHL; and per RANO and mRANO criteria for subjects with GBM [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
2. Phase 1, Part 2: ORR per RECIST v1.1 and modified RECIST for subjects with advanced or metastatic SCCHN and advanced or metastatic NSCLC [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
3. Phase 1, Part 2: Duration of response (DOR) for subjects with advanced or metastatic SCCHN and advanced or metastatic NSCLC [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
4. Phase 1, Part 2: PFS for subjects with advanced or metastatic SCCHN and advanced or metastatic NSCLC [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
5. Phase 2: Duration of response (DOR) [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
6. Phase 2: Duration of disease control, defined as CR, PR, and stable disease (SD) [ Time Frame: Response will be assessed every 8 weeks during study participation which is estimated to be a minimum of 6 months. ]
7. Phase 2: Safety and tolerability measured by the frequency of adverse events (AEs), serious adverse events (SAEs), and deaths [ Time Frame: AEs are assessed for the duration of the study participation which is estimated to be a minimum of 27 months (24 months +100 day safety FU). ]

Eligibility Criteria

• 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

Locations

United States, Alabama

UAB Comprehensive Cancer Center

Birmingham, Alabama, United States, 35294

United States, California

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

USC Norris Cancer Center

Los Angeles, California, United States, 90033

UCSF - University of California San Francisco

San Francisco, California, United States, 94115

United States, Colorado

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States, 80045

United States, Kansas

The University of Kansas Clinical Research Center

Fairway, Kansas, United States, 66205

United States, Maryland

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Lahey Hospital & Medical Center

Burlington, Massachusetts, United States, 01805

United States, New York

NYU Cancer Center

New York, New York, United States, 10016

Columbia University, Herbert Irving Comprehensive Cancer Center

New York, New York, United States, 10032

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Wake Forest Medical Center Boulevard

Winston-Salem, North Carolina, United States, 27157

United States, North Dakota

Sanford Research

Fargo, North Dakota, United States, 58122

United States, Pennsylvania

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States, 15232

United States, South Dakota

Sanford Research

North Sioux City, South Dakota, United States, 57104

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology Research

Austin, Texas, United States, 78705

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Utah

Utah Cancer Specialists

Salt Lake City, Utah, United States, 84106

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Oxford University Hospitals NHS Trust

Oxford, United Kingdom, OX3 7LJ

Sponsors and Collaborators

Incyte Corporation

Bristol-Myers Squibb

Investigators

• 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

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT02327078
• Other Study ID Numbers: INCB 24360-204 / ECHO-204
• First Posted: December 30, 2014
• Last Update Posted: August 28, 2020
• Last Verified: August 2020

Additional relevant 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