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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
325
Anti-PD-1 monoclonal antibody
Honor Health Research Institute
Scottsdale, Arizona, United States
South Texas Accelerated Research Therapeutics
Grand Rapids, Michigan, United States
Rutgers Cancer Institute of Nj
New Brunswick, New Jersey, United States
Carolina Bio-Oncology Institute, Pllc
Huntersville, North Carolina, United States
Houston Methodist Hospital
Houston, Texas, United States
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.
Time frame: 24 months
MTD
Maximum Tolerated Dose of INCMGA00012
Time frame: 24 months
AUC
Area Under the Plasma Concentration versus Time Curve of INCMGA00012
Time frame: 24 months
Cmax
Maximum Plasma Concentration of INCMGA00012
Time frame: 24 months
Tmax
Time to reach maximum (peak) plasma concentration of INCMGA00012
Time frame: 24 months
Ctrough
Trough plasma concentration of INCMGA00012
Time frame: 24 months
Total body clearance of the drug from plasma (CL) of INCMGA00012
Time frame: 24 months
Vss
Apparent volume of distribution at steady state of INCMGA00012
Time frame: 24 months
t1/2
Terminal half-life of INCMGA00012
Time frame: 24 months
ADA
Percent of patients with anti-drug antibody
Time frame: 24 months
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University of Texas Md Anderson Cancer Center
Houston, Texas, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States
Chris Obrien Lifehouse
Camperdown, New South Wales, Australia
St Vincent'S Hospital Sydney
Darlinghurst, New South Wales, Australia
...and 70 more locations