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

Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT02327078
Collaborator
Bristol-Myers Squibb (Industry)
307
24
3
67.4
12.8
0.2

Study Details

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
  • 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
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 :
Nov 26, 2014
Actual Primary Completion Date :
Jul 10, 2020
Actual Study Completion Date :
Jul 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) [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 [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 [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 [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) [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 [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 [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 [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 [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 [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) [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) [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 [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

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Site City State Country Postal Code
1 UAB Comprehensive Cancer Center Birmingham Alabama United States 35294
2 The Angeles Clinic and Research Institute Los Angeles California United States 90025
3 USC Norris Cancer Center Los Angeles California United States 90033
4 UCSF - University of California San Francisco San Francisco California United States 94115
5 University of Colorado Anschutz Medical Campus Aurora Colorado United States 80045
6 The University of Kansas Clinical Research Center Fairway Kansas United States 66205
7 Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21231
8 Dana Farber Cancer Institute Boston Massachusetts United States 02215
9 Lahey Hospital & Medical Center Burlington Massachusetts United States 01805
10 NYU Cancer Center New York New York United States 10016
11 Columbia University, Herbert Irving Comprehensive Cancer Center New York New York United States 10032
12 Duke University Medical Center Durham North Carolina United States 27710
13 Wake Forest Medical Center Boulevard Winston-Salem North Carolina United States 27157
14 Sanford Research Fargo North Dakota United States 58122
15 University of Pittsburgh School of Medicine Pittsburgh Pennsylvania United States 15232
16 Sanford Research North Sioux City South Dakota United States 57104
17 Vanderbilt University Medical Center Nashville Tennessee United States 37232
18 Texas Oncology Research Austin Texas United States 78705
19 MD Anderson Cancer Center Houston Texas United States 77030
20 Utah Cancer Specialists Salt Lake City Utah United States 84106
21 Huntsman Cancer Institute Salt Lake City Utah United States 84112
22 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
23 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
24 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)

More Information

Publications

None provided.
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02327078
Other Study ID Numbers:
  • INCB 24360-204 / ECHO-204
First Posted:
Dec 30, 2014
Last Update Posted:
Aug 28, 2020
Last Verified:
Aug 1, 2020
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 28, 2020