Clinical trial NCT03059823: A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of INCMGA00012 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Solid Tumors
Metastatic Solid Tumors
Keywords: Solid tumors
Metastatic cancer
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03
timeFrame: 24 months
measure: MTD
timeFrame: 24 months
Secondary outcomes:
measure: AUC
timeFrame: 24 months
measure: Cmax
timeFrame: 24 months
measure: Tmax
timeFrame: 24 months
measure: Ctrough
timeFrame: 24 months
measure: Total body clearance of the drug from plasma (CL) of INCMGA00012
timeFrame: 24 months
measure: Vss
timeFrame: 24 months
measure: t1/2
timeFrame: 24 months
measure: ADA
timeFrame: 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Grand Rapids
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of Nj
state: New Jersey
city: Huntersville
country: United States
facility: Carolina Bio-Oncology Institute, Pllc
state: North Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Camperdown
country: Australia
facility: Chris Obrien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent'S Hospital Sydney
state: New South Wales
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis (Uz) Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege - Sart Tilman
city: Burgas
country: Bulgaria
facility: COMPLEX ONCOLOGY CENTER ï¿½ BURGAS EOOD
city: Sofia
country: Bulgaria
facility: Mc Women'S Health-Nadezhda Eood
city: Sofia
country: Bulgaria
facility: Acibadem Cityclinica Mhat Tokuda
city: Sofia
country: Bulgaria
facility: Umhat in Oncology
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital Sun Yat-Sen University
city: Guangzhou
country: China
facility: The First Affiliated Hospital Sun Yat-Sen University
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
city: Wuhan
country: China
facility: Tongji Hospital Huazhong University of Science and Technology
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Zhengzhou
country: China
facility: Henan Cancer Hostipal
city: Helsinki
country: Finland
facility: Docrates Cancer Center
city: Turku
country: Finland
facility: Turku University Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hospital Universitaires de Geneve
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint-Simon
city: Saint-herblain
country: France
facility: Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
city: Toulouse
country: France
facility: Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Charite Mitte
city: Berlin
country: Germany
facility: CHARITE - UNIVERSITï¿½TSMEDIZIN BERLIN
city: Dresden
country: Germany
facility: University Clinic Carl Gustav Carus Technical University Dresden
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Munchen
country: Germany
facility: STADTISCHE KLINIKUM MUNCHEN ï¿½ NEUPERLACH KLINIK FUR HAMATOLOGIE UND ONKOLOGIE
city: Munich
country: Germany
facility: University Hospital Grosshadern Munich
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione Pascale
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Riga
country: Latvia
facility: Riga East University Hospsital
city: Vilnius
country: Lithuania
facility: National Cancer Institute
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Gdynia
country: Poland
facility: SZPITALE WOJEWï¿½DZKIE W GDYNI SPï¿½LKA Z OGRANICZONA ODPOWIEDZIALNOSCIA
city: Krakow
country: Poland
facility: University Hospital Krakow, Department of Oncology
city: Lublin
country: Poland
facility: Ko-Med Centra Kliniczne Osrodek Badan Klinicznych W Lublinie
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Msw Z W-McO W Olsztynie
city: Otwock
country: Poland
facility: Biovirtus Research Site
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Poznan
country: Poland
facility: Katedra I Klinika Onkologii Um W Poznaniu Oddzial Ginekologii Onkologicznej
city: Warsaw
country: Poland
facility: Medical University of Warsaw - 2Nd Department Obstetric and Gynecology
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de La Paz
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (Ciocc)
city: Dnipro
country: Ukraine
facility: Multifield Clinical Hospital No 4
city: Ivano-frankivsk
country: Ukraine
facility: Regional Clinical Oncology Center Facility of State Higher Educational Institution
city: Sumy
country: Ukraine
facility: Rmi Sumy Regional Clinical Oncology Dispensary
city: Uzhgorod
country: Ukraine
facility: Uzhgorod National University Clinical Base Uzhgorod Central City Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Podillia Regional Center of Oncology - Chemotherapy Department
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Sutton
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Chelsea
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: