Clear Cell Renal Cell Carcinoma
Conditions
Keywords
ccRCC, Renal Cell Carcinoma (Kidney Cancer), Renal Cell Carcinoma (RCC), CA9, Actinium, Copper, Theranostics
Brief summary
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.
Interventions
DRUGPD-32766D (a Copper-64 [64Cu] labeled peptide)
After PD-32766D IV injection, undergo a PET/CT scan.
DRUGPD-32766T (an Actinium-225 [225Ac] labeled peptide)
The PD-32766T of the specified dose per cycle is administered intravenously for up to 6 cycles.
Sponsors
PeptiDream Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged ≥18 years. 2. Participants with confirmed diagnosis of ccRCC will be included based on the following characteristics: * 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). 3. Presence of positive tumor uptake 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. 5. The participant's with adequate organ function 6. Life expectancy of at least 12 weeks as assessed by the Investigator.
Exclusion criteria
1. Concurrent serious (as determined by the Investigator), uncontrolled medical conditions, or life-threatening or other significant comorbid conditions. 2. Any chemotherapy, radiotherapy, immunotherapy, major surgery, biologic, investigational or hormonal therapy for treatment of solid tumors within 28 days. 3. Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy. 4. Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months. 5. Any previous CA9 targeting treatment. 6. Known hypersensitivity to the active substance or to any of the excipients of the PD-32766D and or T. 7. Clinically unstable CNS tumor at the time of screening. 8. History of bowel perforation or bowel infarction, history of active stomach or duodenum ulcer or fistula in the last 2 years, history of gastroesophageal reflux disease or enterocolitis Grade ≥3 according to NCI-CTCAE and/or known active gastrointestinal infection, any unresolved prior radiation-induced gastrointestinal injury. 9. Acute infection requiring IV antibiotics, antivirals, or antifungals within 14 days prior to the initiation of treatment (oral treatment are allowed). 10. Pregnant or breastfeeding women. 11. Known active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). 12. Have been diagnosed with another primary malignancy. 13. Have significant, uncontrolled, or active cardiovascular disease 14. Bladder outflow obstruction or unmanageable urinary incontinence. 15. Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 16. Any major surgery within 12 weeks before enrolment. 17. History of psychiatric illness or social situations likely to interfere with ability to comply with protocol required assessment or give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and proportion of participants who experience at least 1 dose-limiting toxicities (DLTs). | Through completion of DLT evaluation (6weeks) | 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). | Through study completion, an average of 6 months. | 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. | Through study completion. an average of 6 months | 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. | Through completion of DLT evaluation (6weeks). | MTD and RDE are determined based on the occurrence of DLTs during the DLT evaluation period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve (AUC) of PD-32766T | Through completion of 6 cycles (each cycle is 4 or 6 weeks) | Pharmacokinetic (PK) parameters based on radioactivity in the blood following the first dose administration of PD-32766T |
| Maximum observed concentration (Cmax) of PD-32766T | Through completion of 6 cycles (each cycle is 4 or 6 weeks) | 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 | Through completion of 6 cycles (each cycle is 4 or 6 weeks) | 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 | Through study completion, an average 6 months. | — |
Countries
United States
Contacts
CONTACTClinical Lead
Outcome results
None listed