A Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive mCRPC

A Prospective, Open-label, Randomized, Phase 1/2 Study of TRC003 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)

The purpose of this study is to evaluate safety and tolerability, pharmacokinetics （PK）, efficacy of TRC003 injection in patients with progressive PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibitor (ARPI) or taxane-based chemotherapy. We plan to recruit 90 participants who will be randomly assigned to 1 of 3 dose cohorts (30 cases per dose cohort) with up to 6 cycles of treatment in this study.

This is a prospective, randomized, open-label, phase 1/2 study on adult patients with PSMA-positive metastatic castration-resistant prostate cancer. Approximately 90 eligible participants will be enrolled and randomized 1:1:1 to three dose cohorts. The first six participants in each cohort will be assessed for dose-limiting toxicity (DLT) during the first treatment cycle.

Each eligible participant will receive one of the predefined doses of TRC003 (7.40, 9.25, 11.10 MBq) by intravenous infusion every 8 weeks (±1 week) for a maximum of 6 cycles if participants benefit from the treatment. All participants in this study may undergo dose modification based on the assessment of safety or efficacy by the investigators.

Any adverse events (AEs) observed or reported will be recorded. Blood and urine samples will be collected after the first administration of TRC003 on 6 participants in each cohort for pharmacokinetics (blood concentration of TRC003). 2 eligible participants of each cohort (total 6 participants) will undergo SPECT/CT for dosimetry after informed consent. All participants will be assessed PSA every 4 weeks. CT with contrast /MRI and bone scan will be evaluated every 8 weeks until proved disease progression by RECIST version 1.1 and the Prostate Cancer Clinical Trials Working Group 3 (PCWG3).

Inclusion Criteria:

• Participants must have the ability to understand and sign ICF.
• Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate.
• Participants must have progressive mCRPC after treatment of ARPI or taxane-based chemotherapy.
• Participant must have been diagnosed with mCRPC with documented progressive disease.
• Participants must have prior orchiectomy and/or ongoing androgen-deprivation therapy with a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).
• Participants must have one or more PSMA-positive lesions whose PSMA uptake (SUVmax) is more than 2 fold of the blood pool.
• Participants with an ECOG performance status of 0 - 2.
• Participants must have adequate organ function
• For participants who have partners of childbearing potential: Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principal Investigator during the study and for 6 months after last investigational product administration.

Exclusion Criteria:

• Participants with mixed histology of prostate cancer (e.g., neuroendocrine).
• Any FDG-positive and PSMA-negative target lesions.
• Any investigational agents and other concurrent chemotherapy, targeted therapy, biologic agents, immunotherapy, radioligand therapy (androgen-deprivation therapy excepted) within 28 days or 5 half-lives prior to day of administration, whichever is longer.
• Previous treatment with any conventional external beam radiotherapy including hemi-body radiation within 6 weeks before enrollment.
• Previous bone-targeted therapy cannot be taken with a stable dose within 4 weeks before enrollment.
• Known hypersensitivity to the components of the study therapy or its analogs.
• Transfusion for the sole purpose of making a participant eligible for study inclusion within 28 days before administration.
• A superscan as seen in the baseline bone scan.
• Concurrent serious (as determined by the Investigator) medical conditions.
• Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment.