An External Control Arm Study Comparing Survival Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With 177Lu-PSMA-617 vs Androgen Receptor Pathway Inhibitor (ARPI) Switch in Routine Care

September 28, 2026 updated by: Novartis Pharmaceuticals

Comparing the Lutetium (177Lu) Vipivotide Tetraxetan Arm of the PSMAfore Clinical Trial to a Switch in Androgen Receptor Pathway Inhibitor (ARPI) as External Control Arm (ECA) Using a Real-world Data Source for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) After Progression on Prior ARPI

The aim of this study is to assess the effectiveness of 177Lu-PSMA-617 (lutetium (177Lu) vipivotide tetraxetan) on survival in patients randomized to receive treatment following progression on one ARPI from the PSMAfore trial compared to the effectiveness of a change in ARPI treatment on survival in a real-world setting in patients with mCRPC who are taxane-naive but have progressed after a switch in ARPI.

Study Overview

Status

Completed

Conditions

Castration-Resistant Prostatic Cancer

Study Type

Observational

Enrollment (Actual)

1525

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Switzerland
- - Basel, Switzerland, CH-4056
    - Novartis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

PSMAfore trial patients with mCRPC who progressed once after treatment with an ARPI and were taxane-naive, and real-world data (RWD) mCRPC patients from the United States (US)-based health research database who were taxane-naive and had evidence of treatment with a change in ARPI immediately following progression.

Description

Inclusion criteria:

Had an International Classification of Diseases, 9th or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM) diagnosis of prostate cancer (PC) (ICD-9-CM 185x or ICD-10-CM C61x).
Had at least two documented clinical visits, on different days, occurring on or after 01 Jan 2013.
Included in probabilistic sample of patients queued for review via abstraction.
Had diagnosis of metastatic disease on or after 01 Jan 2013.
Histology was confirmed as adenocarcinoma of the prostate.
Had confirmed mCRPC diagnosis.
Treated with an ARPI-containing line of therapy (LOT; i.e., index therapy) in the mCRPC setting immediately after progression on one previous ARPI-containing line (in any setting, Hormone Sensitive PC or castration-resistant PC), as defined per the health research database's LOT rules and confirmed via abstraction.
18 years of age or older at the start of index therapy.
Had an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0-1 within 30 days before or up to 7 days after index date, or unknown ECOG PS.

Exclusion criteria:

Female sex.
Had evidence of untreated brain metastases.
Had history of cardiac comorbidities, infection with hepatitis B or C, or spinal cord compression that would indicate significant risk to PSMAfore trial participation.
Diagnosis of an active additional malignancy (i.e., other than prostate cancer).
Evidence of biomarker status that would indicate eligibility for treatment other than ARPI, or better prognosis.
Evidence of prior treatment with therapies that potentially affect study outcomes (e.g., radiopharmaceuticals, taxane, immunotherapy or biological therapy, clinical study drug (CSD), or 177Lu-PSMA-617).
Had evidence of inadequate organ function.
Had evidence of low levels of albumin (< 2.5 g/dL).
Had evidence of a negative PSMA-PET scan.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: COHORT
Time Perspectives: RETROSPECTIVE

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
External Control Arm (ECA) RWD patients with mCRPC who were treated with a change in ARPI after progression on prior ARPI and before taxane treatment.
PSMAfore Trial Treatment Arm (TTA) PSMAfore trial patients with mCRPC who were treated with 177Lu-PSMA-617 after progression on one ARPI.
PSMAfore Trial Control Arm (TCA) PSMAfore trial patients with mCRPC who switched to a subsequent ARPI after progression on a prior ARPI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) of the TTA Group Time Frame: Up to approximately 3 years and 6 months	OS defined as time from randomization to death due to any cause.	Up to approximately 3 years and 6 months
Real-world Overall Survival (rwOS) of the ECA Group (for the Primary Measure) Time Frame: Up to approximately 7 years	rwOS is defined as the time from initiation of the index ARPI to death due to any cause.	Up to approximately 7 years

Secondary Outcome Measures

Outcome Measure	Time Frame
OS of the TCA Group Time Frame: Up to approximately 3 years and 6 months	Up to approximately 3 years and 6 months
rwOS of the ECA Group (for the Secondary Measure) Time Frame: Up to approximately 7 years	Up to approximately 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

<p>Link to study results</p>

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2024

Primary Completion (Actual)

October 1, 2025

Study Completion (Actual)

October 1, 2025

Study Registration Dates

First Submitted

September 21, 2026

First Submitted That Met QC Criteria