A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors

NCT ID: NCT03059823

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 325 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-15
• Study Completion Date: 2024-05-22

Brief Summary

The primary goal of this Phase 1 study is to characterize the safety and tolerability of INCMGA00012 and establish the maximum tolerated dose (MTD) of INCMGA00012 administered on either every two week or every four week schedules of administration among patients with solid tumors. Pharmacokinetics, pharmacodynamics, and the anti-tumor activity of INCMGA00012 will also be assessed.

The purpose of Amendment 5 is to obtain additional safety experience at the newly defined recommended Phase 2 dose of 500 mg every 4 weeks in patients with endometrial cancer, specifically either microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Additionally, every 3 week (Q3W) flat-dosing will be studied in an additional tumor agnostic cohort.

Detailed Description

This study is a Phase 1, open-label, dose escalation and cohort expansion study designed to characterize the safety, tolerability, PK, PD, immunogenicity, and preliminary anti-tumor activity of INCMGA00012 administered IV every 2, 3, or 4 weeks in patients with relapsed/refractory, unresectable locally advanced or metastatic solid tumors.

In the initial phase of the study, two dose schedules will be assessed in dose escalation, once every two weeks and once every four weeks administration of single agent INCMGA00012. Following the establishment of an MTD, additional patients will enroll in expansion cohorts of specific tumor types and/or INCMGA00012 dose.

The Cohort Expansion Phase will include tumor-specific cohorts, consisting of patients with endometrial cancer (unselected [up to n = 35] and MSI-H or dMMR [up to n = 70]), cervical cancer (up to n = 35), sarcoma (up to n = 35), non-small cell lung cancer (NSCLC) (up to n = 35), and 3 cohorts of any tumor histology (tumor-agnostic) (up to n = 15) who will receive flat dosing: 1 cohort treated with INCMGA00012 500 mg Q4W, 1 cohort with INCMGA00012 750 mg Q4W, and 1 cohort treated with INCMGA00012 375 mg Q3W.

Conditions

Locally Advanced Solid Tumors; Metastatic Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation-Q2W

INCMGA00012 treatment once every 2 weeks.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Dose Escalation- Q3W

INCMGA00012 treatment once every 3 weeks.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Dose Escalation- Q4W

INCMGA00012 treatment once every 4 weeks.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Expansion Cohort

INCMGA00012 treatment for locally advanced or metastatic solid tumors.

Group Type: EXPERIMENTAL

retifanlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Interventions

retifanlimab

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

Other Intervention Names

INCMGA0012

Eligibility Criteria

Inclusion Criteria

Histologically proven, locally advanced unresectable or metastatic solid tumors for whom no approved therapy with demonstrated clinical benefit is available or standard treatment was declined. Patients enrolled to Cohort H (endometrial cancer 500 mg Q4W) must have MSI-H or dMMR endometrial cancer, as determined by a local laboratory using IHC or PCR methods and must also have tissue (fresh or archival) available for central confirmation of diagnosis

• Expansion cohort(s): Progression during or following at least 1, and up to 5, previous systemic therapies, consistent with the standard of care for the specific tumor type.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Measurable disease
• Acceptable laboratory parameters

Exclusion Criteria

• Symptomatic central nervous system (CNS) metastases.
• For Cohort Expansion, patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) are not eligible for this study.
• Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring systemic treatment (within the past 2 years), and patients with a history of Grave's disease that are now euthyroid clinically and by laboratory testing.
• Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 4 weeks prior to the initiation of study drug administration.
• Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration.
• Clinically significant cardiovascular disease
• Clinically significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
• Presence of active pneumonitis or history of non-infectious pneumonitis.
• Clinically significant gastrointestinal disorders
• Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days prior to the initiation of study drug. Patients requiring any systemic antiviral, antifungal, or antibacterial therapy for active infection must have completed treatment no less than one week prior to the initiation of study drug
• Known history of positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
• Known history of hepatitis B or hepatitis C infection or known positive test for hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain reaction (PCR)
• Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed
• Dementia or altered mental status that would preclude understanding and rendering of informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Incyte Medical Monitor

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Honor Health Research Institute

Scottsdale, Arizona, United States

South Texas Accelerated Research Therapeutics

Grand Rapids, Michigan, United States

Rutgers Cancer Institute of Nj

New Brunswick, New Jersey, United States

Carolina Bio-Oncology Institute, Pllc

Huntersville, North Carolina, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Texas Md Anderson Cancer Center

Houston, Texas, United States

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Chris Obrien Lifehouse

Camperdown, New South Wales, Australia

St Vincent'S Hospital Sydney

Darlinghurst, New South Wales, Australia

Universitair Ziekenhuis (Uz) Leuven

Leuven, , Belgium

Centre Hospitalier Universitaire de Liege - Sart Tilman

Liège, , Belgium

COMPLEX ONCOLOGY CENTER � BURGAS EOOD

Burgas, , Bulgaria

Mc Women'S Health-Nadezhda Eood

Sofia, , Bulgaria

Acibadem Cityclinica Mhat Tokuda

Sofia, , Bulgaria

Umhat in Oncology

Sofia, , Bulgaria

Peking Union Medical College Hospital

Beijing, , China

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

Peking University Third Hospital

Beijing, , China

Xiangya Hospital Central South University

Changsha, , China

Hunan Cancer Hospital

Changsha, , China

Sun Yat-Sen Memorial Hospital Sun Yat-Sen University

Guangzhou, , China

The First Affiliated Hospital Sun Yat-Sen University

Guangzhou, , China

Qilu Hospital of Shandong University

Jinan, , China

Yunnan Cancer Hospital

Kunming, , China

Zhongda Hospital Southeast University

Nanjing, , China

The Fourth Hospital of Hebei Medical University

Shijiazhuang, , China

The Second Hospital of Shanxi Medical University

Taiyuan, , China

Tongji Hospital Huazhong University of Science and Technology

Wuhan, , China

The First Affiliated Hospital of Xian Jiaotong University

Xi'an, , China

The First Affiliated Hospital of Xiamen University

Xiamen, , China

Henan Cancer Hostipal

Zhengzhou, , China

Docrates Cancer Center

Helsinki, , Finland

Turku University Hospital

Turku, , Finland

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

Centre Antoine Lacassagne

Nice, , France

Hospital Universitaires de Geneve

Paris, , France

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, , France

Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau

Saint-Herblain, , France

Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, , Germany

CHARITE - UNIVERSIT�TSMEDIZIN BERLIN

Berlin, , Germany

University Clinic Carl Gustav Carus Technical University Dresden

Dresden, , Germany

Universitatsklinikum Essen

Essen, , Germany

University Medical Center Freiburg

Freiburg im Breisgau, , Germany

University Hospital Grosshadern Munich

Munich, , Germany

STADTISCHE KLINIKUM MUNCHEN � NEUPERLACH KLINIK FUR HAMATOLOGIE UND ONKOLOGIE

München, , Germany

Azienda Ospedaliero Universitaria Ospedali Riuniti

Ancona, , Italy

Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo

Candiolo, , Italy

Istituto Nazionale Tumori Irccs Fondazione Pascale

Naples, , Italy

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Rome, , Italy

Riga East University Hospsital

Riga, , Latvia

National Cancer Institute

Vilnius, , Lithuania

Auckland City Hospital

Auckland, , New Zealand

Wellington Hospital

Wellington, , New Zealand

SZPITALE WOJEW�DZKIE W GDYNI SP�LKA Z OGRANICZONA ODPOWIEDZIALNOSCIA

Gdynia, , Poland

University Hospital Krakow, Department of Oncology

Krakow, , Poland

Ko-Med Centra Kliniczne Osrodek Badan Klinicznych W Lublinie

Lublin, , Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Msw Z W-McO W Olsztynie

Olsztyn, , Poland

Biovirtus Research Site

Otwock, , Poland

Szpital Kliniczny Przemienienia Panskiego

Poznan, , Poland

Katedra I Klinika Onkologii Um W Poznaniu Oddzial Ginekologii Onkologicznej

Poznan, , Poland

Medical University of Warsaw - 2Nd Department Obstetric and Gynecology

Warsaw, , Poland

Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie

Warsaw, , Poland

Hospital General Universitario Vall D Hebron

Barcelona, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario de La Paz

Madrid, , Spain

Centro Integral Oncologico Clara Campal (Ciocc)

Madrid, , Spain

Multifield Clinical Hospital No 4

Dnipro, , Ukraine

Regional Clinical Oncology Center Facility of State Higher Educational Institution

Ivano-Frankivsk, , Ukraine

Rmi Sumy Regional Clinical Oncology Dispensary

Sumy, , Ukraine

Uzhgorod National University Clinical Base Uzhgorod Central City Clinical Hospital

Uzhhorod, , Ukraine

Podillia Regional Center of Oncology - Chemotherapy Department

Vinnytsia, , Ukraine

Sarah Cannon Research Institute

London, , United Kingdom

The Christie Nhs Foundation Trust Uk

Manchester, , United Kingdom

The Royal Marsden Nhs Foundation Trust - Chelsea

Sutton, , United Kingdom

Countries

United States; Australia; Belgium; Bulgaria; China; Finland; France; Germany; Italy; Latvia; Lithuania; New Zealand; Poland; Spain; Ukraine; United Kingdom

Other Identifiers

2017-000865-63

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCMGA 0012-101

Identifier Type: -

Identifier Source: org_study_id