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

Incyte

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: Nivolumab; Drug: Chemotherapy; Drug: Epacadostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT02327078

INCB 24360-204 / ECHO-204

2016-002423-29 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 307 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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307 participants in 9 patient groups

Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Epacadostat

Drug: Nivolumab

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

Experimental group

Description:

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).

Treatment:

Drug: Chemotherapy

Drug: Epacadostat

Drug: Nivolumab

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

Experimental group

Description:

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).

Treatment:

Drug: Chemotherapy

Drug: Epacadostat

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

Experimental group

Description:

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).

Treatment:

Drug: Chemotherapy

Drug: Epacadostat

Phase 2 Epacadostat 100mg BID + Nivolumab

Experimental group

Description:

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).

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Phase 2 Epacadostat 300mg BID + Nivolumab

Experimental group

Description:

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

Treatment:

Drug: Epacadostat

Drug: Nivolumab