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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03059823
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE February 9, 2017
First Posted Date  ICMJE February 23, 2017
Last Update Posted Date May 30, 2019
Actual Study Start Date  ICMJE November 2016
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: 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 [ Time Frame: 24 months ]
    Maximum Tolerated Dose of INCMGA00012
Original Primary Outcome Measures  ICMJE
 (submitted: February 16, 2017)
  • Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: 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.
  • Maximum Tolerated Dose of MGA012 [ Time Frame: 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • AUC [ Time Frame: 24 months ]
    Area Under the Plasma Concentration versus Time Curve of INCMGA00012
  • Cmax [ Time Frame: 24 months ]
    Maximum Plasma Concentration of INCMGA00012
  • Tmax [ Time Frame: 24 months ]
    Time to reach maximum (peak) plasma concentration of INCMGA00012
  • Ctrough [ Time Frame: 24 months ]
    Trough plasma concentration of INCMGA00012
  • Total body clearance of the drug from plasma (CL) of INCMGA00012 [ Time Frame: 24 months ]
  • Vss [ Time Frame: 24 months ]
    Apparent volume of distribution at steady state of INCMGA00012
  • t1/2 [ Time Frame: 24 months ]
    Terminal half-life of INCMGA00012
  • ADA [ Time Frame: 24 months ]
    Percent of patients with anti-drug antibody
Original Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2017)
  • Area Under the Plasma Concentration versus Time Curve (AUC) of MGA012 [ Time Frame: 24 months ]
  • Maximum Plasma Concentration (Cmax) of MGA012 [ Time Frame: 24 months ]
  • Time to reach maximum (peak) plasma concentration (Tmax) of MGA012 [ Time Frame: 24 months ]
  • Trough plasma concentration (Ctrough) of MGA012 [ Time Frame: 24 months ]
  • Total body clearance of the drug from plasma (CL) of MGA012 [ Time Frame: 24 months ]
  • Apparent volume of distribution at steady state (Vss) of MGA012 [ Time Frame: 24 months ]
  • Terminal half-life (t1/2) of MGA012 [ Time Frame: 24 months ]
  • Percent of patients with anti-drug antibody [ Time Frame: 24 monhts ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of INCMGA00012 in Patients With Advanced Solid Tumors
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Locally Advanced Solid Tumors
  • Metastatic Solid Tumors
Intervention  ICMJE Drug: INCMGA00012
Anti-PD-1 monoclonal antibody
Study Arms  ICMJE
  • Experimental: Dose Escalation-Q2W
    INCMGA00012 treatment once every 2 weeks.
    Intervention: Drug: INCMGA00012
  • Experimental: Dose Escalation- Q3W
    INCMGA00012 treatment once every 3 weeks.
    Intervention: Drug: INCMGA00012
  • Experimental: Dose Escalation- Q4W
    INCMGA00012 treatment once every 4 weeks.
    Intervention: Drug: INCMGA00012
  • Experimental: Expansion Cohort
    INCMGA00012 treatment for locally advanced or metastatic solid tumors.
    Intervention: Drug: INCMGA00012
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 19, 2018)
300
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2017)
125
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 globalmedinfo@incyte.com
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   France,   Germany,   Italy,   New Zealand,   Poland,   Spain,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03059823
Other Study ID Numbers  ICMJE INCMGA 0012-101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Incyte Medical Monitor Incyte Corporation
PRS Account Incyte Corporation
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP