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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Drug: retifanlimab

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.

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 02050
      • Chris OBrien Lifehouse
    • Darlinghurst, New South Wales, Australia, 02010
      • St Vincent's Hospital Sydney
• Belgium
  • Leuven, Belgium, 03000
    • Universitair Ziekenhuis (Uz) Leuven
  • Liege, Belgium, 04000
    • Centre Hospitalier Universitaire de Liege - Sart Tilman
• Bulgaria
  • Burgas, Bulgaria, 08000
    • COMPLEX ONCOLOGY CENTER � BURGAS EOOD
  • Sofia, Bulgaria, 01330
    • Mc Women'S Health-Nadezhda Eood
  • Sofia, Bulgaria, 01407
    • Acibadem Cityclinica Mhat Tokuda
  • Sofia, Bulgaria, 01756
    • Umhat in Oncology
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100000
    • Peking Union Medical College Hospital
  • Beijing, China, 100021
    • Cancer Hospital Chinese Academy of Medical Sciences
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Changsha, China, 410008
    • Xiangya Hospital Central South University
  • Guangzhou, China, 510000
    • Sun Yat-sen Memorial Hospital Sun Yat-sen University
  • Guangzhou, China, 510080
    • The First Affiliated Hospital Sun Yat-Sen University
  • Jinan, China, 250000
    • Qilu Hospital of Shandong University
  • Kunming, China, 650118
    • Yunnan cancer hospital
  • Nanjing, China, 210009
    • Zhongda Hospital Southeast University
  • Shijiazhuang, China, 50010
    • The Fourth Hospital of Hebei Medical University
  • Taiyuan, China, 30001
    • The Second Hospital of Shanxi Medical University
  • Wuhan, China, 430030
    • Tongji Hospital Huazhong University of Science and Technology
  • Xi'an, China, 710061
    • The First Affiliated Hospital of Xian Jiaotong University
  • Xiamen, China, 361000
    • The First Affiliated Hospital of Xiamen University
  • Zhengzhou, China, 450003
    • Henan Cancer Hostipal
• Finland
  • Helsinki, Finland, 00180
    • Docrates Cancer Center
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Bordeaux, France, 33000
    • Institut Bergonié
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75014
    • Hospital Universitaires de Geneve
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesses Croix Saint-Simon
  • Saint-herblain, France, 44800
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Toulouse, France, 31059
    • Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Berlin, Germany, 13353
    • CHARITE - UNIVERSIT�TSMEDIZIN BERLIN
  • Dresden, Germany, 01307
    • University Clinic Carl Gustav Carus Technical University Dresden
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Freiburg, Germany, 79106
    • University Medical Center Freiburg
  • Munchen, Germany, 81737
    • STADTISCHE KLINIKUM MUNCHEN � NEUPERLACH KLINIK FUR HAMATOLOGIE UND ONKOLOGIE
  • Munich, Germany, 81377
    • University Hospital Grosshadern Munich
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
  • Candiolo, Italy, 10060
    • Fondazione Del Piemonte Per L'Oncologia Ircc Candiolo
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Rome, Italy, 00168
    • Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
• Latvia
  • Riga, Latvia, LV1079
    • Riga East University Hospsital
• Lithuania
  • Vilnius, Lithuania, LT-08660
    • National Cancer Institute
• New Zealand
  • Auckland, New Zealand, 01023
    • Auckland City Hospital
  • Wellington, New Zealand, 06021
    • Wellington Hospital
• Poland
  • Gdynia, Poland, 81-519
    • SZPITALE WOJEW�DZKIE W GDYNI SP�LKA Z OGRANICZONA ODPOWIEDZIALNOSCIA
  • Krakow, Poland, 31-501
    • University Hospital Krakow, Department of Oncology
  • Lublin, Poland, 20-362
    • Ko-Med Centra Kliniczne Osrodek Badan Klinicznych W Lublinie
  • Olsztyn, Poland, 10-357
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Msw Z W-McO W Olsztynie
  • Otwock, Poland, 05-400
    • Biovirtus Research Site
  • Poznan, Poland, 06056
    • Szpital Kliniczny Przemienienia Panskiego
  • Poznan, Poland, 60-569
    • Katedra I Klinika Onkologii Um W Poznaniu Oddzial Ginekologii Onkologicznej
  • Warsaw, Poland, 00-315
    • Medical University of Warsaw - 2Nd Department Obstetric and Gynecology
  • Warsaw, Poland, 02-781
    • Centrum Onkologii - Instytut Im. Marii Sklodowskiej - Curie
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • Centro Integral Oncológico Clara Campal (CIOCC)
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
• Ukraine
  • Dnipro, Ukraine, 49102
    • Multifield Clinical Hospital No 4
  • Ivano-frankivsk, Ukraine, 76000
    • Regional Clinical Oncology Center Facility of State Higher Educational Institution
  • Sumy, Ukraine, 40030
    • RMI Sumy Regional Clinical Oncology Dispensary
  • Uzhgorod, Ukraine, 08800
    • Uzhgorod National University Clinical Base Uzhgorod Central City Clinical Hospital
  • Vinnytsia, Ukraine, 21000
    • Podillia Regional Center of Oncology - Chemotherapy Department
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 4BX
    • The Christie Nhs Foundation Trust Uk
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Nhs Foundation Trust - Chelsea
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Honor Health Research Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • South Texas Accelerated Research Therapeutics
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of Nj
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina Bio-Oncology Institute, Pllc
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation-Q2W; INCMGA00012 treatment once every 2 weeks.	Drug: retifanlimab; Anti-PD-1 monoclonal antibody; Other Names: INCMGA0012
Experimental: Dose Escalation- Q3W; INCMGA00012 treatment once every 3 weeks.	Drug: retifanlimab; Anti-PD-1 monoclonal antibody; Other Names: INCMGA0012
Experimental: Dose Escalation- Q4W; INCMGA00012 treatment once every 4 weeks.	Drug: retifanlimab; Anti-PD-1 monoclonal antibody; Other Names: INCMGA0012
Experimental: Expansion Cohort; INCMGA00012 treatment for locally advanced or metastatic solid tumors.	Drug: retifanlimab; Anti-PD-1 monoclonal antibody; Other Names: INCMGA0012

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
MTD	Maximum Tolerated Dose of INCMGA00012	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	Area Under the Plasma Concentration versus Time Curve of INCMGA00012	24 months
Cmax	Maximum Plasma Concentration of INCMGA00012	24 months
Tmax	Time to reach maximum (peak) plasma concentration of INCMGA00012	24 months
Ctrough	Trough plasma concentration of INCMGA00012	24 months
Total body clearance of the drug from plasma (CL) of INCMGA00012		24 months
Vss	Apparent volume of distribution at steady state of INCMGA00012	24 months
t1/2	Terminal half-life of INCMGA00012	24 months
ADA	Percent of patients with anti-drug antibody	24 months

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Incyte Medical Monitor, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2016
• Primary Completion (Estimated): April 27, 2024
• Study Completion (Estimated): April 27, 2024

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Solid tumors; Metastatic cancer
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: INCMGA 0012-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No