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

NCT ID: NCT03126110

Last Updated: 2025-08-14

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

145 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-25

Study Completion Date

2021-11-09

Brief Summary

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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.

Detailed Description

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Conditions

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Advanced Malignancies Metastatic Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W

Participants received INCAGN01876 1.0 milligrams per kilogram (mg/kg) administered intravenously (IV) every 2 weeks (Q2W) in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W

Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, then nivolumab 240 mg Q2W

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 5.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W).

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Ipilimumab

Intervention Type DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Ipilimumab

Intervention Type DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Ipilimumab

Intervention Type DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with nivolumab 3 mg/kg administered IV Q2W and ipilimumab 1 mg/kg administered IV Q6W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Ipilimumab

Intervention Type DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg

Participants with programmed cell death protein/programmed cell death ligand 1 (PD-1/PD-L1) relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Ipilimumab

Intervention Type DRUG

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg

Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg

Participants with squamous cell carcinoma of the head and neck (SCCHN) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg

Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg

Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg

Participants with gastric cancer, squamous cell carcinoma of the head and neck, cervical cancer, or PD-1/PD-L1 relapsed melanoma who had tumor lesions that were amenable to percutaneous biopsy received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Group Type EXPERIMENTAL

INCAGN01876

Intervention Type DRUG

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Nivolumab

Intervention Type DRUG

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Interventions

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INCAGN01876

In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 ().

Intervention Type DRUG

Nivolumab

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Intervention Type DRUG

Ipilimumab

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Biosciences International Sàrl

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John E. Janik, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Washington University - Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer

New York, New York, United States

Site Status

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

University of Oklahoma, Sarah Cannon Research Institute

Oklahoma City, Oklahoma, United States

Site Status

Providance Portland Medical Center

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh, UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, United States

Site Status

Tennessee Oncology, Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

BUMC Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

Site Status

Scientia Clinical Research

Randwick, New South Wales, Australia

Site Status

Greenslopes Private Hospital

Brisbane, Queensland, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Linear Clinical Research

Perth, Western Australia, Australia

Site Status

CHA Centre Hospitalier de l'Ardenne

Libramont, Chevigny, Belgium

Site Status

Saint Augustinus Hospital

Antwerp, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

CHU Brugmann

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Mi Kryviy Rih Center of Dnipropetrovsk Regional Council

Charleroi, , Belgium

Site Status

Ghent University Hospital

Ghent, , Belgium

Site Status

AZ Groeninge

Kortrijk, , Belgium

Site Status

Hospital Clinic I Provincial

Barcelona, , Spain

Site Status

Hospital Clinico y Provincial de Barcelona

Barcelona, , Spain

Site Status

Institut Catala D'Oncologia-Badalona

Barcelona, , Spain

Site Status

Hospital Vall de Hebron

Barcelona, , Spain

Site Status

Hospital Reina Sophia

Córdoba, , Spain

Site Status

University Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Doce de Octubre

Madrid, , Spain

Site Status

Hospital HM Sanchinarro

Madrid, , Spain

Site Status

Clinica Universidad De Navarra (CUN)

Pamplona, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Countries

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United States Australia Belgium Spain

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-004989-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCAGN 1876-201

Identifier Type: -

Identifier Source: org_study_id

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