Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies

The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies in subjects with advanced or metastatic malignancies.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Advanced Malignancies
• Intervention / Treatment: Drug: Nivolumab; Drug: Ipilimumab; Drug: INCAGN01876

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Cancer and Haematology Centre
    • Randwick, New South Wales, Australia, 2148
      • Scientia Clinical Research
  • Queensland
    • Brisbane, Queensland, Australia, 4120
      • Greenslopes Private Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Linear Clinical Research
• Belgium
  • Antwerpen, Belgium, 2610
    • Saint Augustinus Hospital
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1020
    • CHU Brugmann
  • Charleroi, Belgium, 6000
    • Mi Kryviy Rih Center of Dnipropetrovsk Regional Council
  • Ghent, Belgium, 37201
    • Ghent University Hospital
  • Kortrijk, Belgium, 8500
    • Az Groeninge
  • Chevigny
    • Libramont, Chevigny, Belgium, 6800
      • CHA Centre Hospitalier de l'Ardenne
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08036
    • Hospital Clínico y Provincial de Barcelona
  • Barcelona, Spain, 08916
    • Institut Catala D'Oncologia-Badalona
  • Barcelona, Spain
    • Hospital Vall de Hebron
  • Córdoba, Spain, 14004
    • Hospital Reina Sophia
  • Madrid, Spain, 28041
    • Hospital Universitario Doce de Octubre
  • Madrid, Spain, 28034
    • University Hospital Ramon y Cajal
  • Madrid, Spain, 28050
    • Hospital HM Sanchinarro
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra (CUN)
  • Sevilla, Spain, 41015
    • Hospital Universitario Virgen del Rocío
• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 37201
      • Washington University - Siteman Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma, Sarah Cannon Research Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providance Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh, UPMC Cancer Pavilion
  • Tennessee
    • Nashville, Tennessee, United States, 37201
      • Tennessee Oncology, Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75230
      • BUMC Mary Crowley Cancer Research Centers
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Phase 1: Subjects with advanced or metastatic solid tumors.
• Phase 1: Subjects who have disease progression after treatment with available therapies.
• Phase 2: Subjects with advanced or metastatic cervical cancer, gastric cancer (including stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN and PD-1/PD-L1 relapsed melanoma.
• Presence of measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

Exclusion Criteria:

• Laboratory and medical history parameters not within the Protocol-defined range
• Prior treatment with any tumor necrosis factor super family agonist.
• Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
• Active autoimmune disease.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INCAGN01876 + Nivolumab; INCAGN01876 combined with nivolumab.	Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.; Drug: INCAGN01876; In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.
Experimental: INCAGN01876 + Ipilimumab; INCAGN01876 combined with ipilimumab.	Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.; Drug: INCAGN01876; In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.
Experimental: INCAGN01876 + Nivolumab + Ipilimumab; INCAGN01876 combined with nivolumab and ipilimumab.	Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.; Drug: INCAGN01876; In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Phase 1: Safety and tolerability assessed by monitoring frequency, duration, and severity of adverse events (AEs)	An 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 subject provides informed consent.	Screening through 60 days after end of treatment, up to 18 months
Phase 2: Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Defined as the percentage of subjects having complete response (CR) or partial response (PR)	Every 8 weeks for 12 months, then every 12 weeks, up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: ORR based on RECIST v1.1 and modified RECIST v1.1 (mRECIST v1.1)	Defined as the percentage of subjects having CR or PR	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 18 months
Phase 1 & Phase 2: Duration of response based on RECIST v1.1 and mRECIST v1.1	Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause, if occurring sooner than progression.	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 18 months
Phase 1 & Phase 2: Duration of disease control based on RECIST v1.1 and mRECIST v1.1	Defined as CR, PR, and stable disease (SD) as measured from first report of SD or better until disease progression or death from any cause, if occurring sooner than progression.	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 18 months
Phase 1 & Phase 2: Progression-free survival based on RECIST v1.1 and mRECIST v1.1	Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause, if occurring sooner than progression.	Assessed every 8 weeks for 12 months, then every 12 weeks, up to 18 months
Phase 1 & Phase 2: Overall survival	Determined from the start of combination therapy until death due to any cause.	1 year, 2 years, and end of study, up to 24 months
Phase 2: Safety and tolerability assessed by monitoring frequency, duration, and severity of adverse events	An 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 subject provides informed consent.	Screening through 60 days after end of treatment, up to 18 months

Collaborators and Investigators

• Sponsor: Incyte Biosciences International Sàrl
• Investigators: Study Director: John E. Janik, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2017
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): November 9, 2021

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: endometrial cancer; mesothelioma; ovarian cancer; melanoma; hepatocellular carcinoma (HCC); urothelial carcinoma; cervical cancer; renal cell carcinoma (RCC); glucocorticoid-induced tumor necrosis factor receptor (GITR); non-small cell lung cancer (NSCLC); Merkel cell carcinoma; squamous cell carcinoma of the head and neck (SCCHN); small cell lung cancer (SCLC); triple-negative breast cancer (TNBC); gastric cancer (stomach, esophageal, and gastroesophageal junction [GEJ]); microsatellite instability-high (MSI-H) colorectal cancer (CRC)
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: INCAGN 1876-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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