Clinical trial NCT05245006: PET Imaging Study of 89Zr-DFO-YS5 in Men With Prostate Cancer
Official title: A First-in-Human, Pilot PET Imaging Study of 89Zr-DFO-YS5, an immunoPET Agent for Detecting CD46 Positive Malignancy in Men With Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Keywords: First-in-Human
immunoPET agent
CD46 positive malignancy
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Fortis Therapeutics, Inc.
First posted: 2022-02-17
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Optimal time point for imaging using 89Zr-DFO-YS5 PET post-injection (Cohort A)
timeFrame: Up to 7 days
measure: Optimal antibody dose for imaging using 89Zr-DFO-YS5 PET (Cohort B)
timeFrame: Up to 7 days
measure: Proportion of participants with metastatic lesions accurately detected in mCRPC using 89Zr-DFO-YS5 PET (sensitivity) (Cohort C)
timeFrame: Up to 24 months
measure: Median SUVmax (Cohort C)
timeFrame: Up to 24 months
measure: Average SUVmax (SUVmax-ave) (Cohort C)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Proportion of participants with treatment-related Adverse Events
timeFrame: Up to 3 weeks after last dose administration, approximately 35 days
measure: Average organ uptake of 89Zr-DFO-YS5 (Cohort C)
timeFrame: Up to 24 months
measure: Intra-tumoral uptake of 89Zr-DFO-YS5 by tumor type (Cohort C)
timeFrame: Up to 24 months
measure: Intra-tumoral uptake of 89Zr-DFO-YS5 by Site of Disease (Cohort C)
timeFrame: Up to 24 months
measure: Inter-tumoral heterogeneity (Cohort C)
timeFrame: Up to 24 months
measure: Inter-participant heterogeneity (Cohort C)
timeFrame: Up to 24 months
measure: Tumor-to-background signal (Cohort C)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Robert Flavell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: