NPX267 is an antibody drug targeting the inhibitory receptor for B7-H7 (HHLA2) which may control evasion of the immune response in tumors. The goal of this clinical trial is to learn whether NPX267 is safe and tolerable in patients whose cancers are known to express HHLA2 including epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer. The main questions it aims to answer are: * what is an appropriate dose to be given to patients? * are the side effects of treatment manageable? Participants will be evaluated for participation in the study. Patients who are treated will receive an intravenous infusion of NPX267 every three weeks if their disease has not progressed. Patients will be closely monitored by the treating physician.
This trial is divided into two parts. The first part (dose escalation) will test different doses of drug to find a dose for part two. In the second part (dose expansion), more patients will be tested to see if the drug has an effect on patient's tumors. Throughout the study, data will be collected to characterize the clinical activity of the drug. Samples of blood will be taken to help in an understanding of how the drug behaves in the body by assessing the amount of drug in the blood over time (pharmacokinetics), and changes in blood components (pharmacodynamics and safety). Tumor imaging by computed tomography (CT) or magnetic resonance imaging (MRI) will be done about every nine weeks to assess NPX267 impact on tumor growth.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
131
NPX267 will be administered by intravenous infusion every three weeks until documented disease progression or participant withdrawal
Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Albert Einstein Medical College Montefiore Medical Center
New York, New York, United States
Sarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology-San Antonio
San Antonio, Texas, United States
NEXT Oncology-Fairfax
Fairfax, Virginia, United States
Incidence of dose limiting toxicity
Number of subjects with dose limiting toxicity
Time frame: from first dose through 21 days
Incidence of treatment-emergent adverse events
Number and type of adverse events categorized by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: up to 12 weeks from first dose
Number of subjects with tumor response in tumors expressing B7-H7/HHLA2
The proportion of subjects with complete or partial responses or stable disease as defined by RECIST 1.1 criteria
Time frame: up to 12 weeks from first dose
Area under the concentration curve (AUC) of NPX267
Measurement of plasma concentration over time for exposure to NPX267
Time frame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Half-life in circulation (T1/2) of NPX267
Measurement of the clearance of NPX267 from plasma over time
Time frame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Maximum plasma concentration (Cmax) of NPX267
Time frame: Following dosing on day 1, day 22, and day 43 (day 1 of 21-day treatment cycles)
Overall survival
Average length of survival for treated patients
Time frame: From first dose until death from any cause through 30 months
Immunogenicity of NPX267
Number of participants with anti-drug antibodies
Time frame: From first dose through one year
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