A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

The purpose of this study is to find the highest dose level of study drug, CTT1403, that can be safely administered to patients with metastatic castration resistant prostate cancer (mCRPC).

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.

Eligibility Criteria:
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.