Overview
This was a multicenter, open-label, phase I/II study to evaluate the safety and tolerability, radiation dosimetry and pharmacokinetic characteristics, and efficacy of [177Lu] Lu-XT033 injection in patients with metastatic prostate cancer, including a phase I study and a phase II extension study.
Description
The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period.
In phase I,Six subjects were enrolled in the 1.11 Gbq (30 mCi) group of [177Lu] Lu-XT033 Injection. The last subject in this group completed the 4-week observation period after the first dose, With the consent of the Safety Monitoring Committee (SRC), 6 subjects were enrolled in the 1.85 Gbq (50 mCi) group. Both groups used 8 ± 1 weeks as the dosing interval for a total of 4 doses.In phase II,Subjects who met the inclusion and exclusion criteria were treated with [177Lu] Lu-XT033 injection at the recommended phase II dose（RP2D）.After Cycle 4 treatment and prior to Cycle 5 treatment, the investigator assessed the following criteria to determine whether:
The patient showed evidence of response (i.e. radiological, PSA, clinical benefit)
The patient had signs of residual disease on CT with contrast/MRI or bone scan
The patient had shown good tolerance to the [177Lu] Lu-XT033 Injection
If the patient met all of the criteria above and agreed to continue with additional treatment of [177Lu] Lu-XT033, the Investigator could administer 2 additional cycles. A maximum of 6 cycles of [177Lu] Lu-XT033 as allowed.
All subjects continued to undergo safety, tolerability, and efficacy assessments until the study-specified visit occurred or the subject was lost to follow-up or death whichever came first.
Eligibility
Inclusion Criteria:
- Patients must have the ability to understand and sign an approved informed consent form (ICF).
- Patients must be >= 18 and <＝80 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Patients must have a life expectancy >6 months.
- Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive。
- Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
- Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone)； Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens.
- Patients must have progressive mCRPC.
- Patients must have adequate organ function。
- Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, Intra-uterine device（IUD）,etc., during treatment and within 6 months of the last use of the trial drug.
Exclusion Criteria:
- Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.
- Known other malignancies.
- Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment.
- Known hypersensitivity to the components of the study therapy or its analogs.
- A superscan as seen in the baseline bone scan.
- Patients with a history of Central Nervous System (CNS) metastases.
- Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.