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.
Male or female participants aged ≥18 years.
Histological confirmed locally advanced, unresectable, or metastatic ccRCC, after all available standard therapy.
Presence of evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST) guideline (defined by RECIST v1.1).
Presence of positive tumor uptake
Concurrent serious (as determined by the Investigator), uncontrolled medical conditions, or life-threatening or other significant comorbid conditions.
Any chemotherapy, radiotherapy, immunotherapy, major surgery, biologic, investigational or hormonal therapy for treatment of solid tumors within 28 days.
Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy.
Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months.
Sequential
PD-32766D (a Copper-64 [64Cu] labeled peptide)
DrugAfter PD-32766D IV injection, undergo a PET/CT scan.
PD-32766T (an Actinium-225 [225Ac] labeled peptide)
DrugThe PD-32766T of the specified dose per cycle is administered intravenously for up to 6 cycles.
Number and proportion of participants who experience at least 1 dose-limiting toxicities (DLTs).
Number of participants with DLT and DLT rate
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.
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.
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.
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
Maximum observed concentration (Cmax) of PD-32766T
Pharmacokinetic (PK) parameters based on radioactivity in the blood following the first dose administration of PD-32766T
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).
Objective response rate (ORR), Disease control rate (DCR) and Duration of response (DoR) according to RECIST v1.1
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