NCT04647526

Study Evaluating mCRPC Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment

A Phase 3, Open-Label, Randomized Study Evaluating Metastatic Castrate Resistant Prostate Cancer Treatment Using PSMA [Lu-177]-PNT2002 Therapy After Second-line Hormonal Treatment (SPLASH)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 455 (actual)
• Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy and safety of \[Lu-177\]-PNT2002 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with androgen receptor axis-targeted therapy (ARAT).

Detailed description

The primary objective of the study is to determine the efficacy of \[Lu-177\]-PNT2002 (\[Lu-177\]-PSMA-I\&T) versus abiraterone or enzalutamide in delaying radiographic progression in patients with mCRPC. The study consists of 3 phases: Dosimetry, Randomized Treatment, and Long term Follow up. The study will commence with a 25-patient safety and dosimetry lead-in (Part 1) and proceed to a randomization treatment phase in approximately 390 patients (Part 2). Patients in Part 2 will be randomized in a 2:1 ratio to receive either \[Lu-177\]-PNT2002 (Arm A), or enzalutamide or abiraterone (Arm B). Patients in Arm B who experience radiographic progression per central review and meet protocol defined eligibility, may crossover to receive \[Lu-177\]-PNT2002. After final overall survival (OS) analysis, all patients will continue to be followed through Continued Access, including long-term follow-up (LTFU) for at least 5 years from the first therapeutic dose, death, or loss to follow up (Part 3). Only patients that meet PSMA PET avidity criteria per central review will be eligible for this study.

Conditions

• Metastatic Castration-Resistant Prostate Cancer

Interventions

Type	Name	Description
DRUG	[Lu-177]-PNT2002	Participants randomized to Arm A will receive 6.8 GBq (±10%) of \[Lu-177\]-PNT2002 every 8 weeks for 4 cycles
DRUG	Abiraterone	Abiraterone (1000 mg orally once daily with: 5 mg twice daily prednisone or 0.5 mg once daily dexamethasone)
DRUG	Enzalutamide	Enzalutamide (160 mg orally once daily)

Timeline

• Start date: 2021-02-25
• Primary completion: 2023-11-01
• Completion: 2028-03-01
• First posted: 2020-12-01
• Last updated: 2026-01-13
• Results posted: 2026-01-13

Locations

54 sites across 6 countries: United States, Canada, France, Netherlands, Sweden, United Kingdom

Regulatory

• FDA-regulated drug study