A Study of Theranostic Pair PD-32766D/T in Participants With Carbonic Anhydrase IX Positive Clear Cell Renal Cell Carcinoma

Official title

An Open-Label, Multicenter, Phase 1a/1b, Dose Escalation/Dose Expansion Clinical Trial of Theranostic Pair PD-32766D, a 64Cu-Labeled Peptide and PD-32766T, an 225Ac-Labeled Peptide Targeting Carbonic Anhydrase IX in Adult Participants With Relapsed or Refractory Clear Cell Renal Cell Carcinoma Who Have Progressed From or Could Not be Administered Due to Medical Unsuitability or Limited Access to All Standard of Care Therapies

Overview

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

• Drug PD-32766D (a Copper-64 [64Cu] labeled peptide)
  After PD-32766D IV injection, undergo a PET/CT scan.
• Drug PD-32766T (an Actinium-225 [225Ac] labeled peptide)
  The PD-32766T of the specified dose per cycle is administered intravenously for up to 6 cycles.

Primary outcome measures

• Number and proportion of participants who experience at least 1 dose-limiting toxicities (DLTs). [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). [Time frame: Through study completion, an average of 6 months.]
• Incidence of TEAEs leading to dose delay, dose interruption, dose reduction, and/or discontinuation. [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. [Time frame: Through completion of DLT evaluation (6weeks).]

Secondary outcome measures (4)

• Area under the plasma concentration-time curve (AUC) of PD-32766T [Time frame: Through completion of 6 cycles (each cycle is 4 or 6 weeks)]
• Maximum observed concentration (Cmax) 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 [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.]

Eligibility criteria

Inclusion criteria

• Male or female participants aged ≥18 years.
• 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).
• Presence of positive tumor uptake
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
• The participant's with adequate organ function
• Life expectancy of at least 12 weeks as assessed by the Investigator.

Exclusion criteria

• 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.
• Any previous CA9 targeting treatment.
• Known hypersensitivity to the active substance or to any of the excipients of the PD-32766D and or T.
• Clinically unstable CNS tumor at the time of screening.
• 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.
• Acute infection requiring IV antibiotics, antivirals, or antifungals within 14 days prior to the initiation of treatment (oral treatment are allowed).
• Pregnant or breastfeeding women.
• Known active infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
• Have been diagnosed with another primary malignancy.
• Have significant, uncontrolled, or active cardiovascular disease
• Bladder outflow obstruction or unmanageable urinary incontinence.
• Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Any major surgery within 12 weeks before enrolment.
• History of psychiatric illness or social situations likely to interfere with ability to comply with protocol required assessment or give informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Research site — Omaha

Identifiers

NCT: NCT07688187 · PD32766-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗