PET Imaging Study of 89Zr-DFO-YS5 in Men With Prostate Cancer

Robert Flavell, MD, PhD

Status and phase: Active, not recruiting; Phase 1

Conditions: Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

Treatments: Biological: YS5 antibody; Drug: 89Zr-DFO-YS5; Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI); Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; Industry

Identifiers

NCT05245006

209210

NCI-2022-01310 (Registry Identifier)

Details and patient eligibility

About

CD46 is an exciting new therapeutic target in prostate cancer, with the antibody drug conjugate FOR46 under investigation in phase I clinical trials. The hypothesis of the study is that CD46 expression, measured via our novel imaging biomarker, is a characteristic feature of mCRPC, and particularly common in the most lethal forms of the disease including adenocarcinoma and Small-cell neuroendocrine carcinoma (SCNC). These data will provide crucial information about the feasibility of targeting cluster of differentiation 46 (CD46) in mCRPC, will be used guide the development of novel therapeutic and theranostic agents, to help develop treatments that improve outcomes for men with the most lethal forms of prostate cancer.

Full description

This single center imaging study involves one microdose of the imaging agent, followed by whole body PET imaging. Imaging data will be acquired in up to four PET studies to determine tumor and normal tissue uptake and dosimetry.

PRIMARY OBJECTIVES:

1. To determine the optimal time point for imaging (based on analyzing the 4 scans of all participants using 89Zr-DFO-YS5 PET post-injection). (Cohort A)
2. To determine the optimal antibody dose for imaging using 89Zr-DFO-YS5 PET. (Cohort B).
3. To determine the sensitivity of metastatic lesion detection in mCRPC using 89Zr-DFO-YS5 PET as compared with conventional imaging (Cohorts C)

SECONDARY OBJECTIVES:

1. To determine the safety of 89Zr-DFO-YS5.
2. To determine average organ uptake of 89Zr-DFO-YS5 (Cohort C).
3. To descriptively report the patterns of intra-tumoral uptake of 89Zr-DFO-YS5 on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal (Cohorts C).

OUTLINE: Participants were originally assigned to 1 of 3 cohorts. Cohort B is closed to accrual. Enrollment into Cohort A and C are ongoing.

Cohort A: PET imaging data will be acquired up to four times to determine tumor and normal tissue uptake and dosimetry. The optimized scan time will be used for imaging in Cohorts B and C.

(CLOSED) Cohort B: A dose of cold, non-radiolabeled antibody administered will be varied to determine the optimal antibody dose for image quality. The optimized antibody dose will be used in Cohort C. Participants will be followed for an additional 4-5 weeks after dose administration to assess for adverse events.

Cohort C: PET imaging will be acquired at the optimal time point and optimal antibody dose determined in Cohorts A & B, and have the option to obtain an repeat scan at the time of disease progression.

All participants will be followed for up to 5 weeks after their first scan to assess for adverse events and will be followed-up until progression. At the time of progression, participants will have the option to receive a repeat scan.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participants must have histologically or cytologically confirmed metastatic, castration resistant prostate cancer (mCRPC).

2. Age >=18 years

3. Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >60%).

4. Demonstrates adequate organ function as defined below:

   1. Total bilirubin <1.5 X upper limit of normal (ULN).
   2. Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase (SGOT)) <= 3 X institutional upper limit of normal (ULN).
   3. Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) <= 3 X institutional ULN.
   4. Serum creatinine <=1,5 X institutional ULN or calculated creatinine clearance (Glomerular filtration rate (GFR)) >= 60 mL/min, calculated using the Cockcroft-Gault equation.

5. Ability to understand a written informed consent document, and the willingness to sign it.

6. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Exclusion criteria

1. Patients who because of age, general medical, or psychiatric condition, or physiologic status cannot give valid informed consent.
2. Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Cohort A: 89Zr-DFO-YS5

Experimental group

Description:

Participants receive one dose of 89Zr-DFO-YS5 up to 3 millicurie (mCi), and undergo a whole body PET performed at 1-4 hours, approximately 20-28 hours, 48-96 hours, and 120-168 hours post injection for up to 4 scans total. The optimized scan time will be used for imaging in cohorts B and C. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Treatment:

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

Drug: 89Zr-DFO-YS5

Cohort B: 89Zr-DFO-YS5, YS5 antibody

Experimental group

Description:

Participants receive either a 20mg or 50mg dose of YS5 prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. The optimal dose of unmodified YS5 antibody will be used in the following cohorts C \& D. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Treatment:

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

Drug: 89Zr-DFO-YS5

Biological: YS5 antibody

Cohort C: 89Zr-DFO-YS5, Optimal dose YS5 antibody

Experimental group

Description:

Participants receive optimal dose of YS5 antibody prior to imaging and administration of one dose of up to 3 millicurie (mCi) 89Zr-DFO-YS5 and then complete a single whole body PET scan at the optimal time determined in Cohort A. Participants have the option to receive a repeat 89Zr-DFO-YS5 PET at the time of disease progression.

Treatment:

Procedure: Positron Emission Tomography (PET)/Computerized tomography (CT)

Procedure: Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI)

Drug: 89Zr-DFO-YS5

Biological: YS5 antibody