NCT04720157

An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care (SoC), Versus SoC Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

An Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Standard of Care, Versus Standard of Care Alone, in Adult Male Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,145 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: Male
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care (SOC), versus Standard of Care alone, in adult male patients with Metastatic hormone sensitive prostate cancer (mHSPC). In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study. As of 31-Jan-2024, 1144 participants were enrolled in 20 countries.

Detailed description

In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment naïve or minimally treated PSMA-positive mHSPC were to be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617. The primary objective of the study was to determine whether the combination of 177Lu-PSMA-617 + SoC improved radiographic progression free survival (rPFS) over that obtained by administration of SoC alone in mHSPC patients. The randomization was stratified according to the following three factors: disease volume (high v low), age \>= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no). Study duration: approximately 50 months. screening period: after signing ICF, patients were assessed for eligibility and were scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant was randomized via the interactive response technology (IRT) system. Amended protocol v02 included an option for participants to be enrolled into a separate long-term safety follow-up study, and China extension cohort (40 to 60 participants). Amended protocol v03 excluded China extension cohort and added a second 68Ga-PSMA-11 PET/CT scan at rPD. Prior treatment: * Up to 45 days of Luteinizing hormone releasing hormone (LHRH) agonist/antagonists was allowed prior to informed consent form (ICF) signature. If patient did not start the ADT prior randomization, ADT started as soon as possible and ideally no later than 2 weeks after randomization. * Up to 45 days of ARDT was allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT started as soon as possible and ideally no later than 2 weeks after randomization. Patients received ARDT as per label instructions. Randomization period: The participant was randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617. Treatment period: Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients received SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients began 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product was received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles. Patients randomized to the control arm began receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol. The primary endpoint of rPFS was assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician. Participants from both arms also underwent PET/CT scan with 68GaPSMA-11 following Centrally confirmed rPD. An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment. Cross-over period: After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =\< 7 days and enter the Post-treatment Follow-up. Post-Treatment Follow-Up (Safety, Efficacy): After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months. Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first. Survival Follow-Up: After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Conditions

• Prostatic Neoplasms

Interventions

Type	Name	Description
DRUG	177Lu-PSMA-617	administered intravenously once every 6 weeks (1 cycle) for 6 cycles
DRUG	68Ga-PSMA-11	Intravenous dose of approx. 150 Megabecquerel (MBq) at screening and at time of centrally confirmed rPD
DRUG	ARDT	Administered orally on a continuous basis as per package insert and guideline
DRUG	ADT	ADT are administered as per physician order

Timeline

• Start date: 2021-06-09
• Primary completion: 2025-01-13
• Completion: 2027-02-11
• First posted: 2021-01-22
• Last updated: 2026-03-11

Locations

166 sites across 19 countries: United States, Austria, Belgium, Canada, China, Czechia, Denmark, France, Germany, Japan, Netherlands, Poland, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study