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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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03059823
Recruitment Status : Active, not recruiting
First Posted : February 23, 2017
Last Update Posted : September 19, 2022
Information provided by (Responsible Party):
Incyte Corporation

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
Locally Advanced Solid Tumors Metastatic Solid Tumors Drug: retifanlimab 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.

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Study Type : Interventional  (Clinical Trial)
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 : November 15, 2016
Estimated Primary Completion Date : February 27, 2024
Estimated Study Completion Date : February 27, 2024

Arm Intervention/treatment
Experimental: Dose Escalation-Q2W
INCMGA00012 treatment once every 2 weeks.
Drug: retifanlimab
Anti-PD-1 monoclonal antibody
Other Name: INCMGA0012

Experimental: Dose Escalation- Q3W
INCMGA00012 treatment once every 3 weeks.
Drug: retifanlimab
Anti-PD-1 monoclonal antibody
Other Name: INCMGA0012

Experimental: Dose Escalation- Q4W
INCMGA00012 treatment once every 4 weeks.
Drug: retifanlimab
Anti-PD-1 monoclonal antibody
Other Name: INCMGA0012

Experimental: Expansion Cohort
INCMGA00012 treatment for locally advanced or metastatic solid tumors.
Drug: retifanlimab
Anti-PD-1 monoclonal antibody
Other Name: INCMGA0012

Primary Outcome Measures :
  1. 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.

  2. MTD [ Time Frame: 24 months ]
    Maximum Tolerated Dose of INCMGA00012

Secondary Outcome Measures :
  1. AUC [ Time Frame: 24 months ]
    Area Under the Plasma Concentration versus Time Curve of INCMGA00012

  2. Cmax [ Time Frame: 24 months ]
    Maximum Plasma Concentration of INCMGA00012

  3. Tmax [ Time Frame: 24 months ]
    Time to reach maximum (peak) plasma concentration of INCMGA00012

  4. Ctrough [ Time Frame: 24 months ]
    Trough plasma concentration of INCMGA00012

  5. Total body clearance of the drug from plasma (CL) of INCMGA00012 [ Time Frame: 24 months ]
  6. Vss [ Time Frame: 24 months ]
    Apparent volume of distribution at steady state of INCMGA00012

  7. t1/2 [ Time Frame: 24 months ]
    Terminal half-life of INCMGA00012

  8. ADA [ Time Frame: 24 months ]
    Percent of patients with anti-drug antibody

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03059823

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Sponsors and Collaborators
Incyte Corporation
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Study Director: Incyte Medical Monitor Incyte Corporation
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03059823    
Other Study ID Numbers: INCMGA 0012-101
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: September 19, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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