A Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in Taxane Treatment Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer

NCT05658003 | Active Not Recruiting Phase 2

• 1 other identifier: CAAA617B12201
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 15

Brief Summary

The purpose of this study is to evaluate the efficacy of \[177Lu\]Lu-PSMA-617 over a change of androgen receptor-directed therapy (ARDT) treatment in prolonging radiographic progression free survival (rPFS) in Chinese metastatic castration-resistant prostate cancer patients, who were previously treated with another ARDT as last treatment and who have not been exposed to a taxane-containing regimen in castrate resistant prostate cancer (CRPC) or hormone-sensitive prostate cancer (HSPC) settings and who are considered appropriate for delaying taxane-based chemotherapy. The primary endpoint of rPFS will be assessed via blinded independent centralized review of radiographic images provided by the treating physician and as outlined in Prostate Cancer Working Group 3 (PCWG3) guidelines.

Conditions

Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Keywords

Chinese adult male population; therapeutic agent lutetium (177Lu) vipivotide tetraxetan; [177Lu]Lu-PSMA-617; Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer; rPFS; Prostate-specific Membrane Antigen; PSMA

Outcome Measures

Primary Outcomes (1)

• Radiographic progression free survival (rPFS)

  Radiographic progression free survival (rPFS) is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death.

  From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 47 months (estimated final analysis)

Secondary Outcomes (15)

• Overall survival (OS)

  From date of randomization until date of death from any cause, assessed up to 47 months (estimated final analysis)

• Progression Free Survival (PFS)

  From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up to 47 months (estimated final analysis)

• Prostate-specific antigen 50 response rate

  Week 12, Week 24, Week 48

• Time to a first symptomatic skeletal event (TTSSE)

  From date of randomization till date of death from any cause, whichever happens first, assessed up to 47 months (estimated final analysis)

• Time to Prostate Specific Antigen (PSA) progression

  From date of randomization till date of Prostate Specific Antigen (PSA) progression, assessed up to 47 months (estimated analysis)

Study Arms (2)

[177Lu]Lu-PSMA-617

EXPERIMENTAL

Participants will receive 7.4 GBq (200 mCi) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT may be used.

Drug: [177Lu]Lu-PSMA-617; Drug: [68Ga]Ga-PSMA-11; Other: Best supportive care

Androgen receptor-directed therapy (ARDT)

ACTIVE COMPARATOR

For participants randomized to the ARDT arm, the change of ARDT treatment will be administered per the physician's orders. Best supportive care, including ADT may be used.

Drug: ARDT; Drug: [68Ga]Ga-PSMA-11; Other: Best supportive care

Interventions

[68Ga]Ga-PSMA-11 DRUG

single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 259 MBq (3 - 7 mCi).

Androgen receptor-directed therapy (ARDT); [177Lu]Lu-PSMA-617

Best supportive care OTHER

Best supportive/best standard of care as defined by the local investigator

Androgen receptor-directed therapy (ARDT); [177Lu]Lu-PSMA-617

[177Lu]Lu-PSMA-617 DRUG

administered intravenously once every 6 weeks (1 cycle) for 6 cycles

[177Lu]Lu-PSMA-617

ARDT DRUG

administered orally on a continuous basis, as per package insert and guidelines

Also known as: Comparator

Androgen receptor-directed therapy (ARDT)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be Chinese adult men \>= 18 years of age
• Participants must have an ECOG performance status of 0 to 1
• Participant must have histological pathological and/or cytological confirmation of adenocarcinoma of the prostate
• Participants must be \[68Ga\]Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader
• Participants must have a castrate level of serum/plasma testosterone (\< 50 ng/dl, or \< 1.7 nmol/L)
• Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide)) in either HSPC or CRPC setting.
• first generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy
• second generation ARDT must be the most recent therapy received
• candidates for change in ARDT (eligible to receive abiraterone or enzalutamide) as assessed by the treating physician
• Participants cannot have previously progressed nor had intolerable toxicity to both enzalutamide and abiraterone
• Documented progressive mCRPC, based on at least 1 of the following criteria:
• Serum/plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week apart. the minimal start value is 2.0 ng/ml;
• Soft-tissue progression defined based on PCWG3-modified RECIST v1.1(Eisenhauer et al 2009, Scher et al 2016)
• Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria Scher et al 2016)
• Participants must have at least one metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained =\< 28 days prior to randomization

You may not qualify if:

• Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, Lutitium-177, Actium-225, hemi-body irradiation
• Previous PSMA-targeted radioligand therapy
• Prior treatment with PARP inhibitor, cytotoxic chemotherapy for castration resistant or castration sensitive prostate cancer (i.e., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy (including monoclonal antibodies). \[Note: a maximum of 6 cycles of taxane exposure in the adjuvant or neo-adjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neo-adjuvant therapy prior to randomization\]
• Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological, or investigational therapy
• Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
• Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids.
• Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
• Cardiac or cardiac repolarization abnormality, including any of the following:
• History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) and QTc\>=500.
• Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Wuhan, Hubei, 430022, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210006, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

Location

Novartis Investigative Site

Shenyang, Liaoning, 110011, China

Location

Novartis Investigative Site

Xian, Shanxi, 710032, China

Location

Novartis Investigative Site

Xian, Shanxi, 710061, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100034, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Tianjin, 300308, China

Location

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 20, 2022
• Study Start: May 5, 2023
• Primary Completion: December 2, 2024
• Study Completion (Estimated): January 13, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (15)