Phase II Trial to Investigate the Safety and Efficacy of Four Dosing Regimens of OTL78 Injection

Phase II Trial to Investigate the Safety and Efficacy of Four Dosing Regimens of OTL78 Injection (Zopocianine), a Prostate-Specific Membrane Antigen (PSMA)-Targeted Fluorescent Agent, for the Intraoperative Imaging of Prostate Cancer

This study is being done to compare how well Zopocianine (OTL78) in combination with Near InfraRed (NIR) fluorescent imaging may improve the detection of malignant (growing in an uncontrolled way) tissue in adult subjects undergoing prostatectomy and lymph node dissection for biopsy confirmed prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related death behind lung cancer. Prostate cells express Prostate Specific Membrane Antigen (PSMA), which is overexpressed in PCa cells in over 90% of patients. On Target has developed a PSMA-targeted agent, the drug product OTL78, that fluoresces under NIR illumination to help with the identification of prostate cancer tissue during resection surgery that has extended beyond the capsule of the prostate into adjacent tissue and lymph nodes. Intra-operative identification of cancer tissue using real-time imaging modalities that could improve tumor identification, demarcation and lymph node involvement may provide a very useful tool to reduce the frequency of residual cancer and increase complete removal of locally involved lymph nodes. This study is an open label trial of an imaging agent, PSMA targeted fluorescent dye (zopocianine, OTL78), in up to 20 subjects with biopsy confirmed PCa who have been scheduled to undergo a laparoscopic radical prostatectomy with pelvic lymph node dissection in order to explore the relationship between the amount of drug given, the timing of administration relative to surgery, and the utility of the drug in visualizing cancerous tissue during a standard of care radical prostatectomy.

Inclusion Criteria:

1. Provision of signed and dated informed consent and HIPAA form

2. Male subjects 18 years of age and older

3. Known primary prostate cancer and Grade Group 3 to 5 (≥ cT3) or one or more of the following:

   1. Suspected extraprostatic disease (EPD) (extracapsular extension (ECE) and/or seminal vesicle infiltration (SVI)),
   2. 3 or more biopsy cores of grade group 3-5;
   3. Suspected lymph node metastasis (clinical stage cN1, or by magnetic resonance imaging (mriN+), or by Prostate Specific Membrane Antigen positron emission tomography (PSMA PET+));

4. Planned to undergo a standard of care robotic prostatectomy and lymph node dissection

5. Ability to understand the requirements of the study and agree to abide by the study restrictions and to return for the required assessments

6. Agree to use a medically acceptable method of birth control (e.g., spermicide in conjunction with a barrier such as a condom) or sexual abstinence for the duration of the study, including through final study visit (6 weeks) after the dose of study drug. Sperm donation is prohibited during the study and for 3 months after the dose of study drug. Female partners must use hormonal or barrier contraception unless postmenopausal or abstinent.

Exclusion Criteria:

1. The surgeon plans to perform an extraperitoneal approach

2. History of anaphylactic reactions to products containing indocyanine green

3. History of allergy to any of the components of ZOPOCIANINE:

   1. 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA)
   2. Polyethylene glycol-dipeptide linker
   3. Chlorodye

4. Impaired renal or hepatic function:

   1. Renal: creatinine clearance (eGFR) < 50 mL/min
   2. Hepatic: total bilirubin > 2 × upper limit of normal or ALT/AST > 3 × upper limit of normal.

5. Patients with QTc interval ≥ 470 msec per electrocardiogram (ECG) at screening.

6. Significant acute or chronic medical, neurologic, or illness in the subject that, in the judgment of the Principal Investigator, could compromise subject safety, limit the ability to complete the study, and/or compromise the objectives of the study