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

NCT03126110 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: INCAGN 1876-2012016-004989-25
• Study Type: interventional
• Target: 145
• Locations: 4 countries
• Sites: 38

Brief Summary

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.

Conditions

Advanced Malignancies; Metastatic Cancer

Keywords

cervical cancer; endometrial cancer; gastric cancer (stomach, esophageal, and gastroesophageal junction [GEJ]); hepatocellular carcinoma (HCC); melanoma; Merkel cell carcinoma; mesothelioma; microsatellite instability-high (MSI-H) colorectal cancer (CRC); non-small cell lung cancer (NSCLC); ovarian cancer; squamous cell carcinoma of the head and neck (SCCHN); small cell lung cancer (SCLC); renal cell carcinoma (RCC); triple-negative breast cancer (TNBC); urothelial carcinoma; glucocorticoid-induced tumor necrosis factor receptor (GITR)

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

  An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study medication.

  up to approximately 27.4 months

• Phase 2: Objective Response Rate (ORR) Per RECIST v1.1

  ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR), determined by investigator assessment of radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

  up to approximately 44.7 months

Secondary Outcomes (22)

• Phase 1: ORR Per RECIST v1.1

  up to approximately 44.7 months

• Phase 1: ORR Per Modified RECIST (mRECIST) v1.1

  up to approximately 44.7 months

• Phase 2: ORR Per mRECIST v1.1

  up to approximately 44.7 months

• Phase 1: Duration of Response (DOR) Per RECIST v1.1

  up to approximately 44.7 months

• Phase 2: DOR Per RECIST v1.1

  up to approximately 44.7 months

Study Arms (17)

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Ipilimumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Ipilimumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Ipilimumab

Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Ipilimumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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

Drug: INCAGN01876; Drug: Nivolumab

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

EXPERIMENTAL

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.

Drug: INCAGN01876; Drug: Nivolumab

Interventions

INCAGN01876 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 ().

Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab; Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg; Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg

Nivolumab DRUG

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

Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, then nivolumab 240 mg Q2W; Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab; Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg; Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg

Ipilimumab DRUG

Ipilimumab 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; Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab; Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Incyte Biosciences International Sàrl: lead

Study Sites (38)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University - Siteman Cancer Center

St Louis, Missouri, 37201, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer

New York, New York, 10065, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Oklahoma, Sarah Cannon Research Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Providance Portland Medical Center

Portland, Oregon, 97213, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh, UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology, Sarah Cannon Research Institute

Nashville, Tennessee, 37201, United States

Location

BUMC Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

Scientia Clinical Research

Randwick, New South Wales, 2148, Australia

Location

Greenslopes Private Hospital

Brisbane, Queensland, 4120, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Linear Clinical Research

Perth, Western Australia, 6009, Australia

Location

CHA Centre Hospitalier de l'Ardenne

Libramont, Chevigny, 6800, Belgium

Location

Saint Augustinus Hospital

Antwerp, 2610, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

CHU Brugmann

Brussels, 1020, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Mi Kryviy Rih Center of Dnipropetrovsk Regional Council

Charleroi, 6000, Belgium

Location

Ghent University Hospital

Ghent, 37201, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

Hospital Clinico y Provincial de Barcelona

Barcelona, 08036, Spain

Location

Institut Catala D'Oncologia-Badalona

Barcelona, 08916, Spain

Location

Hospital Vall de Hebron

Barcelona, Spain

Location

Hospital Reina Sophia

Córdoba, 14004, Spain

Location

University Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Doce de Octubre

Madrid, 28041, Spain

Location

Hospital HM Sanchinarro

Madrid, 28050, Spain

Location

Clinica Universidad De Navarra (CUN)

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41015, Spain

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Uterine Cervical Neoplasms; Endometrial Neoplasms; Stomach Neoplasms; Carcinoma, Hepatocellular; Melanoma; Carcinoma, Merkel Cell; Mesothelioma; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Squamous Cell Carcinoma of Head and Neck; Small Cell Lung Carcinoma; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Carcinoma, Transitional Cell

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenoma; Neoplasms, Mesothelial; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Neoplasms; Breast Diseases

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

• John E. Janik, MD

  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: April 19, 2017
• First Posted: April 24, 2017
• Study Start: April 25, 2017
• Primary Completion: November 9, 2021
• Study Completion: November 9, 2021
• Last Updated: August 14, 2025
• Results First Posted: December 28, 2022

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); BE (8); ES (10); US (15)