Clinical Trials /

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

NCT03059823

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: INCMGA 0012-101
  • NCT ID: NCT03059823

Conditions

  • Locally Advanced Solid Tumors
  • Metastatic Solid Tumors

Interventions

DrugSynonymsArms
INCMGA00012Dose Escalation-Q2W

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation-Q2WExperimentalINCMGA00012 treatment once every 2 weeks.
  • INCMGA00012
Dose Escalation- Q3WExperimentalINCMGA00012 treatment once every 3 weeks.
  • INCMGA00012
Dose Escalation- Q4WExperimentalINCMGA00012 treatment once every 4 weeks.
  • INCMGA00012
Expansion CohortExperimentalINCMGA00012 treatment for locally advanced or metastatic solid tumors.
  • INCMGA00012

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03
Time Frame:24 months
Safety Issue:
Description: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.

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Solid tumors
  • Metastatic cancer

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