Study of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer

NCT06081686 | Recruiting Phase 1

• 1 other identifier: XT-XTR010-1-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; [177Lu]Lu-XT033 Injection

Outcome Measures

Primary Outcomes (6)

• For phase I:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033 on dose 1.11Gbq and 1.85Gbq

  To evaluate the safety and tolerability of \[177Lu\]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc

  Through study completion, assessed up to 2 years.

• For phase I：Whole body and organ uptake of [177Lu]Lu-XT033 Injection

  Quantitate the absorbed radiation doses (expressed as Gy/MBq) of administered \[177Lu\]Lu-XT033 to kidneys, liver, lungs, spleen, bone/red marrow and salivary glands.

  From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months

• For phase I：Maximum plasma concentration (Cmax) of Lutetium [Lu 177] Lu-XT033 in patients.

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.

  From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months

• For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.

  From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months

• 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.

  Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC0-168 will be listed and summarized using descriptive statistics.

  From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months

• For phase II:Prostate-specific Antigen 50 (PSA50) Response

  PSA50 response was defined as the proportion of participants who had a \>= 50% decrease in PSA from baseline confirmed by a PSA measurement \>= 4 weeks later.

  Through study completion, assessed up to 2 years.

Secondary Outcomes (11)

• For phase I:Prostate-specific Antigen 50 (PSA50) Response

  Through study completion, assessed up to 2 years.

• For phase I/II:Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level(PCWG3)

  Through study completion, assessed up to 2 years.

• For phase I/II:Time to PSA progression

  Through study completion, assessed up to 2 years.

• For phase I/II:Radiographic Progression-free Survival (rPFS)

  Through study completion, assessed up to 2 years.

• For phase I/II:Overall Response Rate (ORR)

  Through study completion, assessed up to 2 years.

Study Arms (2)

Phase I:[177Lu]Lu-XT033 Injection

EXPERIMENTAL

During dose verification phase,Patients received \[177Lu\]Lu-XT033 Injection 1.11Gbq（30mCi）/1.85Gbq（50mCi）intravenously every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Drug: Phase I:[177Lu]Lu-XT033 Injection

Phase II:[177Lu]Lu-XT033 Injection

EXPERIMENTAL

During dose expansion phase,patients received \[177Lu\]Lu-XT033 Injection at R2PD based on phase I.

Drug: Phase II:[177Lu]Lu-XT033 Injection

Interventions

Phase I:[177Lu]Lu-XT033 Injection DRUG

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 .

Phase I:[177Lu]Lu-XT033 Injection

Phase II:[177Lu]Lu-XT033 Injection DRUG

Patients received \[177Lu\]Lu-XT033 Injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Phase II:[177Lu]Lu-XT033 Injection

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sinotau Pharmaceutical Group: lead

Study Sites (2)

Peking University Cancer Hospital

Beijing, Beijing Municipality, 100042, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Dingwei Ye

  Fudan University

  PRINCIPAL INVESTIGATOR

• Zhi Yang

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shan Zhang

CONTACT

010-52805710; zhangshan@sinotau.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2023
• First Posted: October 13, 2023
• Study Start: September 13, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)