A Study of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of Epacadostat (INCB024360) in Combination With Durvalumab (MEDI4736) in Subjects With Selected Advanced Solid Tumors (ECHO-203)

The purpose of this study is to explore the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of INCB024360 administered in combination with MEDI4736 in subjects with selected advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Lung Cancer; Solid Tumors; UC (Urothelial Cancer)
• Intervention / Treatment: Drug: MEDI4736; Drug: INCB024360

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States
  • Colorado
    • Denver, Colorado, United States
  • Florida
    • Miami, Florida, United States
    • Port Saint Lucie, Florida, United States
    • Sarasota, Florida, United States
    • Tampa, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • North Carolina
    • Durham, North Carolina, United States
    • Huntersville, North Carolina, United States
    • Winston-Salem, North Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects, age 18 years or older
• Histologically or cytologically confirmed diagnosis of selected locally advanced or metastatic solid tumors
• Must have failed at least 1 prior treatment regimen for locally advanced or metastatic disease or be intolerant to treatment or refuse standard treatment

Exclusion Criteria:

• Laboratory and medical history parameters not within protocol-defined range
• Participation in any other study in which receipt of an investigational study drug occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose
• Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor (exception is tumor types in which a PD-1 pathway targeted agent is approved, e.g. melanoma, non-small cell lung cancer.)
• Receipt of any anticancer medication in the 21 days prior to receiving the first dose of study medication
• Has an active or inactive autoimmune process
• Evidence of interstitial lung disease or active, non-infectious pneumonitis
• Prior radiotherapy within 2 weeks of initiating treatment; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis
• Untreated central nervous system (CNS) metastases or CNS metastases that have progressed
• Currently pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI4736 + INCB024360; MEDI4736 at selected dose levels every 2 weeks + INCB024360 25 mg BID as starting dose, followed by dose escalations until MTD or PAD is identified	Drug: MEDI4736; MEDI4736 administered intravenously (IV) every two weeks (q2w); Drug: INCB024360; INCB024360: Oral daily dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 : Number of Treatment-Emergent Adverse Events (TEAE)	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment	Duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Phase 2: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	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.	Measured every 8 weeks for duration of study treatment [approximately 12 months]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Objective Response Rate (ORR) as Determined by Radiographic Disease Assessments Per Modified RECIST v1.1	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	Measured every 8 weeks for duration of study treatment [approximately 6 months]
Phase 2: Number of Treatment-Emergent Adverse Events	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment	Continuously for duration of study treatment and up to 90 days after the last dose [approximately 3 years]
Phase 1 and 2: Durability of Response as Measured by the Time From the Earliest Date of Disease Response Until Earliest Date of Disease Progression	Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression.	Measured every 8 weeks for duration of active study treatment [approximately 24 months]
Phase 1 and 2: Progression-free Survival as Measured by the Duration From the Date of Enrollment Until the Earliest Date of Disease Progression or Death		Measured every 8 weeks for duration of active study treatment [approximately 24 months]
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Peak Concentration		Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Measured by Time to Maximal Observed Concentration		Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Phase 1 and 2: Pharmacokinetics (PK) of INCB024360 as Area Under the Concentration-time Curve		Pre dose, 0.5, 1,2, 4.6.& 8 hrs Post dose on C1D1,C1D8,C2D1
Phase 1 and 2: Immunogenicity of MEDI4736 as Measured by the Number and Percentage of Subjects Who Develop Detectable Anti-drug Antibodies (ADAs)		Measured at defined study visits from Cycle 1 Day 1 through cycle 2 [approximately 2 weeks].

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Collaborators: AstraZeneca

Publications and helpful links

General Publications

• Naing A, Algazi AP, Falchook GS, Creelan BC, Powderly J, Rosen S, Barve M, Mettu NB, Triozzi PL, Hamm J, Zhou G, Walker C, Dong Z, Patel MR. Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors. Cancer. 2023 Jan 1;129(1):71-81. doi: 10.1002/cncr.34512. Epub 2022 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2015
• Primary Completion (Actual): August 28, 2019
• Study Completion (Actual): October 16, 2020

Study Registration Dates

• First Submitted: November 19, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: INCB 24360-203 / ECHO-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No