This is an open-label, multicenter, Phase 1a/1b study evaluating the theranostic pair 64Cu-PD-32766 Injection (PD-32766D) and 225Ac-PD-32766 Injection (PD-32766T) in adult patients with relapsed or refractory Carbonic Anhydrase IX (CA9)-expressing clear cell renal cell carcinoma (ccRCC). The primary objective is to evaluate the safety and tolerability of PD-32766T, and to characterize its pharmacokinetics and preliminary antitumor activity. Participants will first undergo imaging with PD-32766D to assess CA9 expression. Subjects with positive tumor uptake will be eligible to receive PD-32766T. In Phase 1a, PD-32766T will be administered in an escalating dose levels and schedule determined according to protocol and Safety Review Committee recommendations. In Phase 1b, participants will receive PD-32766T at the recommended dose and schedule identified from Phase 1a to further evaluate safety, tolerability, and preliminary efficacy. A total of up to 60 participants will be enrolled in the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
After PD-32766D IV injection, undergo a PET/CT scan.
The PD-32766T of the specified dose per cycle is administered intravenously for up to 6 cycles.
Research site
Omaha, Nebraska, United States
RECRUITINGNumber and proportion of participants who experience at least 1 dose-limiting toxicities (DLTs).
Number of participants with DLT and DLT rate
Time frame: Through completion of DLT evaluation (6weeks)
Incidence, intensity, seriousness, and causality of adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse event of special interest (AESI) and serious adverse events (SAEs).
Number and proportion of participants with AEs, TEAEs, AESI and SAEs.
Time frame: Through study completion, an average of 6 months.
Incidence of TEAEs leading to dose delay, dose interruption, dose reduction, and/or discontinuation.
Number and proportion of participants with TEAEs leading to dose delay, dose interruption, dose reduction, and/or discontinuation as a measure of tolerability.
Time frame: Through study completion. an average of 6 months
Maximum tolerated dose (MTD) and the recommended dose for expansion (RDE) of PD-32766T based on dose-limiting toxicities.
MTD and RDE are determined based on the occurrence of DLTs during the DLT evaluation period.
Time frame: Through completion of DLT evaluation (6weeks).
Area under the plasma concentration-time curve (AUC) of PD-32766T
Pharmacokinetic (PK) parameters based on radioactivity in the blood following the first dose administration of PD-32766T
Time frame: Through completion of 6 cycles (each cycle is 4 or 6 weeks)
Maximum observed concentration (Cmax) of PD-32766T
Pharmacokinetic (PK) parameters based on radioactivity in the blood following the first dose administration of PD-32766T
Time frame: Through completion of 6 cycles (each cycle is 4 or 6 weeks)
Urine PK profile of PD-32766T after IV injection
Radioactivity in the urine following the first dose administration: amount, cumulative amount, and fraction of the dosed radioactivity excreted in urine (Fe).
Time frame: Through completion of 6 cycles (each cycle is 4 or 6 weeks)
Objective response rate (ORR), Disease control rate (DCR) and Duration of response (DoR) according to RECIST v1.1
Time frame: Through study completion, an average 6 months.
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