A Trial of CTT1403 for Metastatic Castration Resistant Prostate Cancer

Phase 1

Completed

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Dose Escalation	CTT1403	Escalating doses of 0.75 GBq - 2.0 GBq of CTT1403
Dose Escalation	CTT1057	Escalating doses of 0.75 GBq - 2.0 GBq of CTT1403
Dose Escalation	68Ga-PSMA-11	Escalating doses of 0.75 GBq - 2.0 GBq of CTT1403
Dose Escalation/Expansion	CTT1403	Escalating doses of 3.0 GBq - 9.0 GBq of CTT1403
Dose Escalation/Expansion	CTT1057	Escalating doses of 3.0 GBq - 9.0 GBq of CTT1403
Dose Escalation/Expansion	68Ga-PSMA-11	Escalating doses of 3.0 GBq - 9.0 GBq of CTT1403

Primary Outcome Measures

Name	Time	Method
Frequency of Dose-limiting Toxicity at Escalating Dose Levels of CTT1403	6-8 weeks from time of injection on Cycle 1 - Day 1	The dose-limiting toxicity was defined as any of the following: 1. Grade 4 neutropenia lasting \> 5 consecutive days 2. Grade 3 or 4 febrile neutropenia 3. Grade 4 thrombocytopenia lasting ≥ 7 days, or Grade 3 or 4 thrombocytopenia with clinically significant bleeding or requirement for platelet transfusion 4. Any nonhematologic, treatment-related AE ≥ Grade 3, with the exceptions of Grade 3 nausea, vomiting, diarrhea, non-clinically significant electrolyte abnormality, constipation, fever, fatigue, or skin rash that resolves to Grade ≤ 2 within 72 hours with optimal medical management 5. Any other treatment-related toxicity that results in delay of Cycle 2 administration of CTT1403 by \> 21 days and/or toxicity considered by the Investigator and Sponsor's medical representatives to be dose-limiting.
Objective Response Rate by RECIST v1.1 Criteria	Cycle 1-Day 35, Cycle 2-Day 35, 30 Days After Last Dose, 8 Weeks Post-Treatment. Each cycle lasted 35 days.	Changes in only the largest diameters (unidimensional measurment) of the tumor lesions are used in the RECIST v1.1 criteria. Data presented as RECIST Overall Response.

Secondary Outcome Measures

Name	Time	Method
Assessment of Organ Dosimetry of CTT1403 by SPECT/CT Imaging	2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1	Organ dosimetry was assessed via SPECT/CT imaging until two imaging periods have been collected in which study drug cannot be detected by SPECT/CT. Time points included (2 hrs ± 1 followed by 24±12 hrs, 48±12 hrs, and 168±24 hrs post-infusion on Cycle 1-Day 1. Data calculated using OLINDA. Absorbed dose is calculated as single value wherein absorbed dose is proportional to the integral of activity over time.
Assessment of Pharmacokinetics of CTT1403	Samples were collected during Cycle 1 (timepoints start at the initiation of infusion): Day 1 (30 min +/- 5 min and 2 hrs +/- 30 min), Day 2 (24 hrs +/- 12 hrs), Day 3 (48 hrs +/- 12 hrs), Day 8 (168 hrs +/- 24 hrs), Day 15 (336 hrs +/- 24 hrs)	The distribution half-life and the elimination half-life of CTT1403 were calculated.
Number of Participants With Change in Patient Reported Pain as Measured by Brief Pain Index	Cycle 1-Day 1 and Cycle 2-Day 1. Each cycle lasted 35 days.	The Brief Pain Index uses a scale of 0-10 to rate the severity of pain. A rating of 0 indicates no pain. A rating of 10 indicates the worst pain imaginable.