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

Sponsor
Incyte Corporation (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03059823
Collaborator
(none)
325
Enrollment
80
Locations
4
Arms
87.4
Anticipated Duration (Months)
4.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
325 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of INCMGA00012 in Patients With Advanced Solid Tumors
Actual Study Start Date :
Nov 15, 2016
Anticipated Primary Completion Date :
Feb 27, 2024
Anticipated Study Completion Date :
Feb 27, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. MTD [24 months]

      Maximum Tolerated Dose of INCMGA00012

    Secondary Outcome Measures

    1. AUC [24 months]

      Area Under the Plasma Concentration versus Time Curve of INCMGA00012

    2. Cmax [24 months]

      Maximum Plasma Concentration of INCMGA00012

    3. Tmax [24 months]

      Time to reach maximum (peak) plasma concentration of INCMGA00012

    4. Ctrough [24 months]

      Trough plasma concentration of INCMGA00012

    5. Total body clearance of the drug from plasma (CL) of INCMGA00012 [24 months]

    6. Vss [24 months]

      Apparent volume of distribution at steady state of INCMGA00012

    7. t1/2 [24 months]

      Terminal half-life of INCMGA00012

    8. ADA [24 months]

      Percent of patients with anti-drug antibody

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Incyte Corporation

    Investigators

    • Study Director: Incyte Medical Monitor, Incyte Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT03059823
    Other Study ID Numbers:
    • INCMGA 0012-101
    First Posted:
    Feb 23, 2017
    Last Update Posted:
    Jun 28, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Incyte Corporation
    Solid tumors
    Metastatic cancer
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Jun 28, 2022