This is a first-in-human, Phase 1/2, open-label, study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Mavrostobart (PT199) alone and in combination with a PD-1 inhibitor or chemotherapy.
Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action and is expected to completely inhibit CD73 enzyme activity. Mavrostobart (PT199) is designed to counter the adenosine-mediated immunosuppressive tumor microenvironment, rendering anti-tumor immune cells to be more active and more responsive to checkpoint immunotherapies, such as PD-1/PD-L1 inhibitors. CD73 is widely overexpressed in a number of different cancers, including pancreatic ductal adenocarcinoma (PDAC), gastric carcinoma, colorectal carcinoma, non-small cell lung cancer (NSCLC), sarcomas and glioblastomas. Thus, targeting CD73 may provide benefit for patients with a high CD73 expression in their tumor. Mavrostobart (PT199) addresses the limitations of current CD73 inhibitors and is expected to increase antitumor immune activation, especially in combination with PD-1 pathway inhibition, and thus offer a new treatment option for cancer patients. NSCLC is known to have a high expression level of CD73, and emerging clinical data has shown that targeting CD73 may provide clinical benefit, when combined with an immune checkpoint inhibitor (ICI) and/or standard of care chemotherapies to overcome treatment resistance.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Mavrostobart (PT199) is an anti-CD73 mAb with a differentiated mechanism of action.
Anti-PD-1 monoclonal antibody 200 mg Q3W, inhibits the lymphocytes PD-1 receptors, blocking the ligands that would deactivate it and prevent an immune response.
Dosing is per Standard of Care.
Carolina BioOncology Institute
Huntersville, North Carolina, United States
RECRUITINGSarah Cannon Research Institute University of Oklahoma
Oklahoma City, Oklahoma, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
To determine the maximum tolerated dose (MTD), if reached.
Time frame: Start of the study drug till 90 days after last dose.
Recommended Phase 2 Dose of Mavrostobart (PT199) as a single agent and/or in combination with a PD-1 inhibitor.
Time frame: Start of the study drug till 90 days after last dose.
Dose Limiting Toxicity (DLT).
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
Preliminary efficacy assessed by the response rate by RECIST 1.1 for overall response rate.
Time frame: Start of the study drug till 90 days after last dose.
Area Under the Curve from time 0 to last (AUC0-last) of Mavrostobart (PT199)
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
Maximum Concentration (Cmax) of Mavrostobart (PT199)
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
Half Life (T1/2) of Mavrostobart (PT199)
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
Preliminary efficacy assessed by the response rate by RECIST 1.1 for disease control rate.
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
Progression free survival duration.
Time frame: Time Frame: Start of the study drug till 90 days after last dose.
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Dosing is per Standard of Care.
Dosing is per Standard of Care.
Dosing is per Standard of Care.
Dosing is per Standard of Care.
Dosing is per Standard of Care.
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGTranquility Research
Webster, Texas, United States
RECRUITINGNEXT Oncology
Fairfax, Virginia, United States
RECRUITING6-month overall survival.
Time frame: Time Frame: Start of the study drug till 90 days after last dose.