A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors
- Conditions
- Locally Advanced Solid TumorsMetastatic Solid Tumors
- Interventions
- Registration Number
- NCT03059823
- Lead Sponsor
- Incyte Corporation
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 325
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation-Q2W retifanlimab INCMGA00012 treatment once every 2 weeks. Dose Escalation- Q3W retifanlimab INCMGA00012 treatment once every 3 weeks. Dose Escalation- Q4W retifanlimab INCMGA00012 treatment once every 4 weeks. Expansion Cohort retifanlimab INCMGA00012 treatment for locally advanced or metastatic solid tumors.
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 24 months Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
MTD 24 months Maximum Tolerated Dose of INCMGA00012
- Secondary Outcome Measures
Name Time Method t1/2 24 months Terminal half-life of INCMGA00012
Ctrough 24 months Trough plasma concentration of INCMGA00012
AUC 24 months Area Under the Plasma Concentration versus Time Curve of INCMGA00012
Cmax 24 months Maximum Plasma Concentration of INCMGA00012
Tmax 24 months Time to reach maximum (peak) plasma concentration of INCMGA00012
Total body clearance of the drug from plasma (CL) of INCMGA00012 24 months Vss 24 months Apparent volume of distribution at steady state of INCMGA00012
ADA 24 months Percent of patients with anti-drug antibody
Trial Locations
- Locations (79)
Szpital Kliniczny Przemienienia Panskiego
🇵🇱Poznan, Poland
Medical University of Warsaw - 2Nd Department Obstetric and Gynecology
🇵🇱Warsaw, Poland
Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie
🇵🇱Warsaw, Poland
St Vincent'S Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
The Fourth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, China
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
Chris Obrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Docrates Cancer Center
🇫🇮Helsinki, Finland
Turku University Hospital
🇫🇮Turku, Finland
Tongji Hospital Huazhong University of Science and Technology
🇨🇳Wuhan, China
Henan Cancer Hostipal
🇨🇳Zhengzhou, China
Institut Gustave Roussy
🇫🇷Villejuif, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
SZPITALE WOJEW�DZKIE W GDYNI SP�LKA Z OGRANICZONA ODPOWIEDZIALNOSCIA
🇵🇱Gdynia, Poland
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
🇩🇪Berlin, Germany
University Hospital Grosshadern Munich
🇩🇪Munich, Germany
Institut Bergonie
🇫🇷Bordeaux, France
Centre Leon Berard
🇫🇷Lyon, France
STADTISCHE KLINIKUM MUNCHEN � NEUPERLACH KLINIK FUR HAMATOLOGIE UND ONKOLOGIE
🇩🇪Munchen, Germany
Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
🇫🇷Saint-herblain, France
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
National Cancer Institute
🇱🇹Vilnius, Lithuania
Wellington Hospital
🇳🇿Wellington, New Zealand
Riga East University Hospsital
🇱🇻Riga, Latvia
Biovirtus Research Site
🇵🇱Otwock, Poland
Katedra I Klinika Onkologii Um W Poznaniu Oddzial Ginekologii Onkologicznej
🇵🇱Poznan, Poland
CHARITE - UNIVERSIT�TSMEDIZIN BERLIN
🇩🇪Berlin, Germany
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
University Medical Center Freiburg
🇩🇪Freiburg, Germany
Hospital Universitario de La Paz
🇪🇸Madrid, Spain
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Multifield Clinical Hospital No 4
🇺🇦Dnipro, Ukraine
Auckland City Hospital
🇳🇿Auckland, New Zealand
The Christie Nhs Foundation Trust Uk
🇬🇧Manchester, United Kingdom
Azienda Ospedaliero Universitaria Ospedali Riuniti
🇮🇹Ancona, Italy
Istituto Nazionale Tumori Irccs Fondazione Pascale
🇮🇹Naples, Italy
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
🇮🇹Rome, Italy
Peking University Third Hospital
🇨🇳Beijing, China
Yunnan Cancer Hospital
🇨🇳Kunming, China
The Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xi'an, China
Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
🇫🇷Toulouse, France
The Royal Marsden Nhs Foundation Trust - Chelsea
🇬🇧Sutton, United Kingdom
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Mc Women'S Health-Nadezhda Eood
🇧🇬Sofia, Bulgaria
Rutgers Cancer Institute of Nj
🇺🇸New Brunswick, New Jersey, United States
Carolina Bio-Oncology Institute, Pllc
🇺🇸Huntersville, North Carolina, United States
Universitair Ziekenhuis (Uz) Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liege - Sart Tilman
🇧🇪Liege, Belgium
Acibadem Cityclinica Mhat Tokuda
🇧🇬Sofia, Bulgaria
COMPLEX ONCOLOGY CENTER � BURGAS EOOD
🇧🇬Burgas, Bulgaria
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
Umhat in Oncology
🇧🇬Sofia, Bulgaria
Beijing Cancer 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
Qilu Hospital of Shandong University
🇨🇳Jinan, China
The First Affiliated Hospital Sun Yat-Sen University
🇨🇳Guangzhou, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, China
Hospital Universitaires de Geneve
🇫🇷Paris, France
Groupe Hospitalier Diaconesses Croix Saint-Simon
🇫🇷Paris, France
Centre Antoine Lacassagne
🇫🇷Nice, France
University Clinic Carl Gustav Carus Technical University Dresden
🇩🇪Dresden, Germany
Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo
🇮🇹Candiolo, Italy
Rmi Sumy Regional Clinical Oncology Dispensary
🇺🇦Sumy, Ukraine
Centro Integral Oncologico Clara Campal (Ciocc)
🇪🇸Madrid, Spain
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Msw Z W-McO W Olsztynie
🇵🇱Olsztyn, Poland
University Hospital Krakow, Department of Oncology
🇵🇱Krakow, Poland
Ko-Med Centra Kliniczne Osrodek Badan Klinicznych W Lublinie
🇵🇱Lublin, Poland
Uzhgorod National University Clinical Base Uzhgorod Central City Clinical Hospital
🇺🇦Uzhgorod, Ukraine
Regional Clinical Oncology Center Facility of State Higher Educational Institution
🇺🇦Ivano-frankivsk, Ukraine
Podillia Regional Center of Oncology - Chemotherapy Department
🇺🇦Vinnytsia, Ukraine
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
Zhongda Hospital Southeast University
🇨🇳Nanjing, China