This is an open label Phase 1, first-in-human (FIH) study of TST005, a bi-specific antibody consisting of a PD-L1 monoclonal antibody (mAb) and a transforming growth factor beta (TGF-β) trap in subjects with locally advanced or metastatic cancers
The study has 2 parts. Part A is a dose escalation portion where the patients will be doses every three weeks following an accelerated 3+3 design. This portion will enroll approximately 25 patients with locally advanced or metastatic cancers. Part B is an expansion portion where approximately 30 additional patients will be dosed at the recommended dose level every 3 weeks. This part will include patients with locally advanced or metastatic HPV related malignancies. The trial will last approximately 2 years, with assessments including safety labs, ECGs, PKs and PDs and CT/MRI tumor assessments, based on the Q3W dosing schedule.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
TST005 is a bifunctional human immunoglobulin G1 (IgG1) monoclonal
Gabrail Cancer Center
Canton, Ohio, United States
Mary Crowley Cancer Research
Dallas, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Part A - Determine the maximum tolerated dose (MTD) or recommended Phase 2 dose(s) (RP2D)
As measured by the number of participants experiencing a dose limiting toxicity (DLT) in each dosing cohort
Time frame: Up to 90 days following last dose
Part B - Patient safety as characterized by frequency and severity of adverse events
Characterize the safety profile of TST005 including the frequency and severity of treatment-emergent adverse events.
Time frame: Up to 90 days following last dose
Part A - Area under Plasma concentration vs. time curve (AUC) for TST005
Observe changes in AUC over time
Time frame: Up to 90 days following last dose
Part A - Peak Plasma concentration (Cmax) for TST005
Observe the maximum serum concentration
Time frame: Up to 90 days following last dose
Part A - Time to maximum observed serum (Tmax) for TST005
Tmax is the time in hours / days for TST005 to reach the maximum concentration after administration
Time frame: Up to 90 days following last dose
Part A - Terminal half-life of TST005
Time for serum level to decrease by 1/2 during the terminal elimination phase
Time frame: Up to 90 days following last dose
Immunogenicity of TST005
To determine if the formation of Anti-drug antibodies (ADA) or neutralizing antibodies (NAb) against TST005 are observed
Time frame: Up to 90 days following last dose
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Part B - Assess the Objective response rate (ORR) of TST005
as measured by RECIST v 1.1 and iRECIST
Time frame: Up to 90 days following last dose
Part B - Assess the Disease Control rate (DCR) of TST005
Percentage of patients that exhibit stable disease (SD), + partial response (PR), + complete response (CR)
Time frame: Up to 90 days following last dose
Part B - Assess the Duration of Response of TST005
Measured by the time a patient shows response
Time frame: Up to 90 days following last dose
Part B - Assess the Time to Response (TTR) of TST005
Measured by the average time patients show a response to TST005
Time frame: Up to 90 days following last dose
Part B - Assess the Progression -free Survival (PFS) of TST005
Measured by the average time before patients show signs of disease progression after receiving TST005
Time frame: Up to 90 days following last dose
Part B - Assess the Overall Survival (OS) of TST005
Time between treatment of TST005 and death for any reason
Time frame: Up to 90 days following last dose