A Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Participants With Advanced or Metastatic Malignancies (ECHO-208)

Incyte

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Lirilumab; Drug: Ipilimumab; Drug: Nivolumab; Drug: Epacadostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03347123

2017-001743-12 (EudraCT Number)

INCB 24360-208 (ECHO-208)

Details and patient eligibility

About

The purpose of this study is to determine the safety, tolerability, and efficacy of epacadostat when given in combination with nivolumab and ipilimumab, and in combination with nivolumab and lirilumab, in participant with advanced or metastatic malignancies.

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• During Phase 1, participant with locally advanced or metastatic solid tumors with disease progression on or after treatment with available therapies, or who are intolerant to treatment, or who refuse standard treatment.
• During Phase 2, participant with advanced cancer who have received at least one prior therapy or are treatment naive, depending on the specified tumor type.
• Presence of measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of ≥ 12 weeks.

Exclusion criteria

• Laboratory and medical history parameters not within the Protocol-defined range.
• Receipt of anticancer medications or investigational drugs within Protocol-defined time frames.
• Previous radiotherapy within 7 days of Cycle 1 Day 1.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Prior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.
• Active infection requiring systemic therapy.
• Any active or inactive autoimmune disease or syndrome

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 7 patient groups

Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID

Experimental group

Description:

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Ipilimumab

Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID

Experimental group

Description:

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of each 14 day cycle and ipilimumab 1 mg/kg intravenous (IV) every 6 weeks thereafter on Day 1 of every third treatment cycle until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Ipilimumab

Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID

Experimental group

Description:

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 50 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Lirilumab

Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID

Experimental group

Description:

Participants with advanced or metastatic solid tumor who have received no more than 2 prior treatment regimens received epacadostat 100 mg BID orally in combination with nivolumab 240 mg on day 1 of every 14 day cycle and lirilumab 240 mg IV every 4 weeks until disease progression or occurrence of unacceptable drug-related toxicities or discontinuation or up to 24 months.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Lirilumab

Phase 2: Dose Expansion: Treatment Group A: Cohort A1

Experimental group

Description:

Participants with unresectable or metastatic melanoma (MEL) were planned to be included in this cohort, who did not receive prior systemic therapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Ipilimumab

Phase 2: Dose Expansion: Treatment Group A: Cohort A2

Experimental group

Description:

Participants with advanced or metastatic non-small cell lung cancer (NSCLC) were planned to be included in this cohort, who have received no more than 1 prior line of platinum-based chemotherapy for advanced or metastatic disease to receive epacadostat in combination with nivolumab and ipilimumab at the MTD/PAD determined from dose escalation phase.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Ipilimumab

Phase 2: Dose Expansion: Treatment Group B: Cohort B1

Experimental group

Description:

Participants with recurrent or metastatic serotonin norepinephrine reuptake inhibitor (SCCHN) were planned to be included in this cohort, who received no more than 1 prior line of platinum-based chemotherapy for recurrent or metastatic disease to receive epacadostat in combination with nivolumab and lirilumab at the MTD/PAD determined from dose escalation phase.

Treatment:

Drug: Epacadostat

Drug: Nivolumab

Drug: Lirilumab