A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

This is a Phase 1, first-in-human dose escalation/dose expansion study evaluating escalating doses of CTT1403 in patients with PSMA-avid mCRPC with progressive disease on at least one androgen signaling inhibitor, followed by a dose expansion to further evaluate the safety, tolerability, efficacy and biological activity of CTT1403. CTT1403 is a PSMA-targeted 177Lu-labeled radiotherapy being developed for prostate cancer with a unique PSMA binding scaffold and an albumin binding moiety to extend circulation half-life. The PSMA binding scaffold is shared with CTT1057, a PSMA-specific PET diagnostic imaging agent shown in Phase 1 clinical trials to be specifically taken up by PSMA+ tumor. PSMA PET imaging by CTT1057 will be used diagnostically to select patients with PSMA-avid disease for treatment. The purpose of this study is to identify the dose limiting toxicity and recommended phase 2 dose of CTT1403. Eligible participants with demonstrated therapeutic benefit will be offered a second dose of study drug.

Inclusion criteria

• Patients must have histologically confirmed prostate adenocarcinoma that is metastatic and castration resistant (mCRPC).
• At least 3 metastatic foci avid for PSMA-specific PET agent (CTT1057) uptake on Screening PSMA PET.
• Has received docetaxol, ineligible for docetaxol, or refused docetaxol for the treatment of prostate cancer.
• Has progression by the PCWG3 criteria during or after treatment with either abiraterone or enzalutamide
• Male Age ≥ 18 years.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix 2).
• Demonstrate adequate organ function

Exclusion criteria

• Has received previous treatment with radium-223 or another radiopharmaceutical within 3 months prior to first dose of CTT1403.
• Has received prior systemic anti-cancer therapy (excluding radiopharmaceutical) within 14 days, or 5 half-lives, whichever is shorter, prior to first dose of CTT1403.
• Has received external-beam radiation within 14 days prior to first dose of CTT1403.
• Has received cabazitaxel for the treatment of mCRPC.
• Has received previous treatment with a therapeutic targeting PSMA.
• Has an additional active malignancy requiring therapy that may confound the assessment of the study endpoints.
• Has clinically significant cardiovascular disease
• Has a history of untreated brain metastases
• Has evidence of diffuse bone marrow involvement by prostate cancer in the judgment of study investigator.
• Clinically significant urinary obstruction or moderate/severe hydronephrosis on baseline imaging.
• Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before CTT1403 administration.
• Has known positive status for chronic hepatitis B or hepatitis C
• Known or suspected myelodysplastic syndrome.
• Has any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.