Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer in Japan

NCT05114746 | Active Not Recruiting Phase 2

• 1 other identifier: CAAA617A11201
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to assess the efficacy, tolerability, safety, pharmacokinetic (PK) and dosimetry of 177Lu-PSMA-617, in participants with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in Japan. Furthermore, the safety, PK and dosimetry of 68Ga-PSMA-11 (PSMA imaging agent) are assessed in the same study. Another purpose of this study is to provide humanistic perspective access to study treatment (68Ga-PSMA-11 and 177Lu-PSMA-617) for the eligible patients with PSMA-positive mCRPC until marketed products are available in Japan. Furthermore, if data availability PK and dose rate of 177 Lu-PSMA-617 will be evaluated to refine discharge criteria in Japan. After obtaining manufacturing and marketing approval in Japan, this clinical trial will continue as a post marketing trial.

Conditions

Prostate Cancer

Keywords

177Lu-PSMA-617; 68Ga-PSMA-11; 68Ge/68Ga Generator; metastatic castration-resistant prostate cancer; mCRPC; prostate-specific membrane antigen; PSMA; radioligand; taxane; enzalutamide; abiraterone; Overall Response Rate; ORR

Outcome Measures

Primary Outcomes (2)

• Part 1 (safety run-in part): Dose Limiting Toxicity (DLT) during 1 cycle (6 weeks)

  A Dose Limiting Toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to 177Lu-PSMA-617 while fulfilling one of the criteria as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Cycle 2 Day 1 (Day 42)

• Part 2 (Post-taxane part) and Part 3 (Pre-taxane part): Overall Response Rate (ORR) based on local assessment

  Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) according to PCWG3 modified RECIST 1.1.

  From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years

Secondary Outcomes (37)

• Part 2 and Part 3 (main part): Overall Survival (OS)

  From date of the first administration of 177Lu-PSMA-617 until date of death from any cause, assessed up to 2 years

• Part 2 and Part 3 (main part): Radiographic Progression-Free-Survival (rPFS) based on local assessment

  From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years

• Part 2 and Part 3 (main part): Overall Response Rate (ORR) based on central review

  From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years

• Part 2 and Part 3 (main part): Disease Control Rate (DCR) as per central and local review

  From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years

• Part 2 and Part 3 (main part): Duration of Response (DOR) based on local imaging

  From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to 2 years

Study Arms (1)

177Lu-PSMA-617

EXPERIMENTAL

PSMA positivity will be confirmed by PET/CT scan after administration of 68Ga-PSMA-11. All eligible participants will receive recommended dose of 177Lu-PSMA-617 via intravenous injection every 6 weeks (+/- 1 week) for a maximum of 6 cycles.

Radiation: 177Lu-PSMA-617; Radiation: 68Ga-PSMA-11; Other: Best supportive/best standard of care

Interventions

177Lu-PSMA-617 RADIATION

administered intravenously at a dose of 7.4 GBq (+/- 10%). 7.4 GBq dose is equivalent to 200 mCi or 7400 MBq.

177Lu-PSMA-617

68Ga-PSMA-11 RADIATION

68Ga-PSMA-11 is manufactured by radiolabeling of PSMA-11 precursor with 68Ga directly at clinical trial sites immediately prior to administration into participants. The 68Ga used for radiolabeling will be eluted from the 68Ge/68Ga generator. 68Ga-PSMA-11 will be prepared as a sterile solution and administered intravenously at a dose of 111 - 259 MBq (3 - 7 mCi).

177Lu-PSMA-617

Best supportive/best standard of care OTHER

Best supportive/best standard of care as defined by the local investigator (Post taxane population only)

177Lu-PSMA-617

Eligibility Criteria

• Age: 20 Years - 100 Years
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG performance status:
• Post-taxane population only: 0 to 2.
• Pre-taxane population only: 0 to 1.
• Participants must have a previous histological, pathological, and/or cytological confirmation of prostate cancer.
• Part 1/2/3 only; Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the sponsor's central reader, before the enrollment to 177Lu-PSMA-617 treatment period.
• Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the local investigator, before the enrollment to 177Lu-PSMA-617 treatment period.
• Participants must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
• Post-taxane population only: Participants must have received at least one ARDT (for example enzalutamide, abiraterone, apalutamide, or darolutamide, etc.) in either the hormone-sensitive/castrate-resistant or non-metastatic/metastatic prostate cancer setting.
• Pre-taxane population only: Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide) and be a candidate for change in ARDT as assessed by the treating physician.
• 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.
• Post-taxane population only: Participants must have been previously treated with at least 1, but no more than 2 prior taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a participant has received only 1 taxane regimen, the participant is eligible if :
• a. The participant's physician deems him unsuitable to receive a second taxane regimen (e.g., frailty assessed by geriatric or health status evaluation or intolerance, etc.).
• Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
• Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression.

You may not qualify if:

• Previous treatment with any of the following within 6 months of the enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted therapy is not allowed.
• Post-taxane population: Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\], ARDT is not included) within 28 days prior to day of the enrollment.
• Pre-taxane population: Prior treatment with PARP inhibitor, cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy \[including monoclonal antibodies\]) \[Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy\]
• Known hypersensitivity to the components of 177Lu-PSMA-617, 68Ga-PSMA-11 or excipients or to drugs of similar classes.
• Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitors, biological, AKT inhibitors or investigational therapy.
• Participants with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Eckert & Ziegler Radiopharma GmbH: collaborator

Study Sites (8)

Novartis Investigative Site

Kashiwa, Chiba, 277-8577, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 0608648, Japan

Location

Novartis Investigative Site

Kobe, Hyōgo, 6500047, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa-ku, 236-0004, Japan

Location

Novartis Investigative Site

Chiba, 260-8717, Japan

Location

Novartis Investigative Site

Fukushima, 9601295, Japan

Location

Novartis Investigative Site

Ishikawa, 9208641, Japan

Location

Novartis Investigative Site

Kyoto, 606-8507, Japan

Location

Related Publications (1)

• Takano S, Inaki A, Hirata K, Sparks RB, Sato M, Nomura S, Hattori T, Kambara H, Nguyen Q, Shiga T, Kinuya S, Hosono M. Pharmacokinetics and dosimetry of [177Lu]Lu-PSMA-617 and [68Ga]Ga-PSMA-11 in Japanese patients with PSMA-positive mCRPC. Ann Nucl Med. 2025 Nov;39(11):1201-1212. doi: 10.1007/s12149-025-02079-8. Epub 2025 Jul 10.

  PMID: 40638023 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Pluvicto; gallium 68 PSMA-11

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

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: November 10, 2021
• Study Start: January 25, 2022
• Primary Completion: December 8, 2023
• Study Completion (Estimated): June 25, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (8)