Clinical trial NCT06081686: Study of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
Official title: Phase I/II Study to Evaluate the Safety and Tolerability, Radiation Dosimetry and Pharmacokinetics, and Efficacy of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
[177Lu]Lu-XT033 Injection
Lead sponsor: Sinotau Pharmaceutical Group
Sponsor class: INDUSTRY
First posted: 2023-10-13
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: Inclusion Criteria:

1. Patients must have the ability to understand and sign an approved informed consent form (ICF).
2. Patients must be \>= 18 and \<＝80 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Patients must have a life expectancy \>6 months.
5. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
6. Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive。
7. Patients must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
8. 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.
9. Patients must have progressive mCRPC.
10. Patients must have adequate organ function。
11. 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:

1. 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.
2. Known other malignancies.
3. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment.
4. Known hypersensitivity to the components of the study therapy or its analogs.
5. A superscan as seen in the baseline bone scan.
6. Patients with a history of Central Nervous System (CNS) metastases.
7. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.

Primary outcomes:
measure: For phase I:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033 on dose 1.11Gbq and 1.85Gbq
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I：Whole body and organ uptake of [177Lu]Lu-XT033 Injection
timeFrame: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
measure: For phase I：Maximum plasma concentration (Cmax) of Lutetium [Lu 177] Lu-XT033 in patients.
timeFrame: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
measure: For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.
timeFrame: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
measure: For phase I：Area Under plasma concentration-time Curve from time 0 to 168 hours (AUC0-168) of Lutetium [Lu 177] Lu-XT033 in patients.
timeFrame: From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
measure: For phase II:Prostate-specific Antigen 50 (PSA50) Response
timeFrame: Through study completion, assessed up to 2 years.
Secondary outcomes:
measure: For phase I:Prostate-specific Antigen 50 (PSA50) Response
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level(PCWG3)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Time to PSA progression
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Radiographic Progression-free Survival (rPFS)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Overall Response Rate (ORR)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II: Duration of Response (DOR)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Disease Control Rate (DCR)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Health related quality of life(HRQOL)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Time to First Symptomatic Skeletal Event (SSE)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase I/II:Overall Survival (OS)
timeFrame: Through study completion, assessed up to 2 years.
measure: For phase II:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033
timeFrame: Through study completion, assessed up to 2 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Dingwei Ye
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Cancer Hospital & Institute
name: Zhi Yang
role: PRINCIPAL_INVESTIGATOR
References: