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

Metastatic Solid Tumors Clinical Trial

Official title:

A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of INCMGA00012 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03059823
• Other study ID #: INCMGA 0012-101
• Status: Completed
• Phase: Phase 1
• Start date: November 15, 2016
• Est. completion date: May 22, 2024

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 325
• Est. completion date: May 22, 2024
• Est. primary completion date: May 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Locally Advanced Solid Tumors
• Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• retifanlimab
Anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
Australia	Chris Obrien Lifehouse	Camperdown	New South Wales
Australia	St Vincent'S Hospital Sydney	Darlinghurst	New South Wales
Belgium	Universitair Ziekenhuis (Uz) Leuven	Leuven
Belgium	Centre Hospitalier Universitaire de Liege - Sart Tilman	Liege
Bulgaria	COMPLEX ONCOLOGY CENTER � BURGAS EOOD	Burgas
Bulgaria	Acibadem Cityclinica Mhat Tokuda	Sofia
Bulgaria	Mc Women'S Health-Nadezhda Eood	Sofia
Bulgaria	Umhat in Oncology	Sofia
China	Beijing Cancer Hospital	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Hunan Cancer Hospital	Changsha
China	Xiangya Hospital Central South University	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
Finland	Docrates Cancer Center	Helsinki
Finland	Turku University Hospital	Turku
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	Centre Antoine Lacassagne	Nice
France	Groupe Hospitalier Diaconesses Croix Saint-Simon	Paris
France	Hospital Universitaires de Geneve	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
Germany	CHARITE - UNIVERSIT�TSMEDIZIN BERLIN	Berlin
Germany	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin
Germany	University Clinic Carl Gustav Carus Technical University Dresden	Dresden
Germany	Universitatsklinikum Essen	Essen
Germany	University Medical Center Freiburg	Freiburg
Germany	STADTISCHE KLINIKUM MUNCHEN � NEUPERLACH KLINIK FUR HAMATOLOGIE UND ONKOLOGIE	Munchen
Germany	University Hospital Grosshadern Munich	Munich
Italy	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
Latvia	Riga East University Hospsital	Riga
Lithuania	National Cancer Institute	Vilnius
New Zealand	Auckland City Hospital	Auckland
New Zealand	Wellington Hospital	Wellington
Poland	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	Katedra I Klinika Onkologii Um W Poznaniu Oddzial Ginekologii Onkologicznej	Poznan
Poland	Szpital Kliniczny Przemienienia Panskiego	Poznan
Poland	Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie	Warsaw
Poland	Medical University of Warsaw - 2Nd Department Obstetric and Gynecology	Warsaw
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal (Ciocc)	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Paz	Madrid
Ukraine	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	Uzhgorod
Ukraine	Podillia Regional Center of Oncology - Chemotherapy Department	Vinnytsia
United Kingdom	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 States	South Texas Accelerated Research Therapeutics	Grand Rapids	Michigan
United States	Houston Methodist Hospital	Houston	Texas
United States	University of Texas Md Anderson Cancer Center	Houston	Texas
United States	Carolina Bio-Oncology Institute, Pllc	Huntersville	North Carolina
United States	Rutgers Cancer Institute of Nj	New Brunswick	New Jersey
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03	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.	24 months
Primary	MTD	Maximum Tolerated Dose of INCMGA00012	24 months
Secondary	AUC	Area Under the Plasma Concentration versus Time Curve of INCMGA00012	24 months
Secondary	Cmax	Maximum Plasma Concentration of INCMGA00012	24 months
Secondary	Tmax	Time to reach maximum (peak) plasma concentration of INCMGA00012	24 months
Secondary	Ctrough	Trough plasma concentration of INCMGA00012	24 months
Secondary	Total body clearance of the drug from plasma (CL) of INCMGA00012		24 months
Secondary	Vss	Apparent volume of distribution at steady state of INCMGA00012	24 months
Secondary	t1/2	Terminal half-life of INCMGA00012	24 months
Secondary	ADA	Percent of patients with anti-drug antibody	24 months