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

NCT03347123 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: INCB 24360-208 (ECHO-208)2017-001743-12
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Solid Tumors

Keywords

Epacadostat; nivolumab; ipilimumab; lirilumab; solid tumor; melanoma; non-small cell lung cancer (NSCLC); squamous cell carcinoma of the head and neck (SCCHN); IDO inhibitor

Outcome Measures

Primary Outcomes (2)

• Phase 1: Percentage of Participants With At Least One Treatment Emergent Adverse Events (TEAEs)

  A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment. AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.

  Screening through up to 100 days after end of treatment, up to approximately 24 months

• Phase 2: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  ORR was defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Secondary Outcomes (6)

• Phase 1: Objective Response Rate (ORR) Based on RECIST v1.1

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

• Phase 1: Duration of Response (DOR)

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

• Phase 1: Progression-free Survival (PFS)

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

• Phase 2: Duration of Response (DOR)

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

• Phase 2: Progression-free Survival (PFS)

  Every 8 weeks for the first 12 months and then every 12 weeks thereafter up to end of treatment (Up to Month 24)

Study Arms (7)

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Lirilumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Lirilumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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.

Drug: Epacadostat; Drug: Nivolumab; Drug: Lirilumab

Interventions

Epacadostat DRUG

Phase 1: Epacadostat at the protocol-defined dose twice daily. Phase 2: Epacadostat at the recommended dose from Phase 1.

Also known as: INCB024360

Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID; Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID; Phase 2: Dose Expansion: Treatment Group A: Cohort A1; Phase 2: Dose Expansion: Treatment Group A: Cohort A2; Phase 2: Dose Expansion: Treatment Group B: Cohort B1

Nivolumab DRUG

Nivolumab at the protocol-specified dose and schedule.

Also known as: Opdivo®, BMS-936558

Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID; Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID; Phase 2: Dose Expansion: Treatment Group A: Cohort A1; Phase 2: Dose Expansion: Treatment Group A: Cohort A2; Phase 2: Dose Expansion: Treatment Group B: Cohort B1

Ipilimumab DRUG

Ipilimumab at the protocol-specified dose and schedule.

Also known as: Yervoy®, BMS-734016

Phase 1: Dose Escalation: Treatment Group A: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group A: Cohort 2 Epacadostat 100 mg BID; Phase 2: Dose Expansion: Treatment Group A: Cohort A1; Phase 2: Dose Expansion: Treatment Group A: Cohort A2

Lirilumab DRUG

Lirilumab at the protocol-specified dose and schedule.

Also known as: IPH2102, BMS-986015

Phase 1: Dose Escalation: Treatment Group B: Cohort 1 Epacadostat 50 mg BID; Phase 1: Dose Escalation: Treatment Group B: Cohort 2 Epacadostat 100 mg BID; Phase 2: Dose Expansion: Treatment Group B: Cohort B1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

epacadostat; Nivolumab; Ipilimumab; lirilumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Medical Monitor Consultant for Incyte

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 20, 2017
• Study Start: March 21, 2018
• Primary Completion: January 29, 2021
• Study Completion: January 29, 2021
• Last Updated: February 28, 2022
• Results First Posted: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)