A Study of the Safety, Tolerability, and Efficacy of Epacadostat Administered in Combination With Nivolumab in Select Advanced Cancers (ECHO-204)
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 |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: (Phase 1, Part 1) : Nivolumab + Epacadostat
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Drug: Nivolumab (Phase 1)
specified dose and dosing schedule
Drug: Epacadostat (Phase 1)
oral twice daily continuous at the protocol-defined dose
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Experimental: (Phase 2): Nivolumab + Epacadostat
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Drug: Nivolumab (Phase 2)
specified dose and dosing schedule
Drug: Epacadostat (Phase 2)
oral twice daily continuous at the protocol-defined dose
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Experimental: (Phase 1, Part 2): Nivolumab + Epacadostat + Chemotherapy
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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
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Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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
Inclusion Criteria:
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Male or female subjects, age 18 years or older
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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
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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.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
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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:
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Laboratory and medical history parameters not within Protocol-defined range
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Currently pregnant or breastfeeding
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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
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Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
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Subjects with any active or inactive autoimmune process
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Evidence of interstitial lung disease or active, noninfectious pneumonitis
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Subjects with any active or inactive autoimmune process
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Ocular MEL
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- INCB 24360-204 / ECHO-204