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

Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Completed
Sponsor
Incyte Corporation

Study Contact

For general questions about clinical trials, contact Research Support Services at (615) 322-7343 or research.support.services@vumc.org