An International Prospective 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)

An estimated 1.3 million new cases of prostate cancer (PC) and 359,000 cancer
deaths were attributed to PC in 2018 worldwide (International Agency for
Research on Cancer 2018) and a majority of patients who die of prostate cancer
will pass through the metastatic hormone sensitive prostate cancer (mHSPC)
phase of the disease. Historically mHSPC has been treated, since the discovery
of its hormone dependence in the 1940s, with surgical or medical castration
resulting in frequent and rapid palliative benefits and a presumptive
improvement in cancer-specific and overall survival. Attempts to improve
survival and quality of life have included, but have not been limited to,
earlier use of androgen deprivation therapy (ADT) for asymptomatic advanced
disease, use of traditional anti-androgens to achieve combined androgen
blockade (Prostate Cancer Trialists' Collaborative 2000), intermittent androgen
therapy (Hussain et al 2013), early bisphosphonate use (Dearnaley et al 2009,
James et al 2016b, James et al 2016a, Smith et al 2014), gonadotropin releasing
hormone antagonists, targeted biologic agents (Yu et al 2015) and
radiopharmaceuticals (Bilen et al 2014, James et al 2016a) with either absent,
limited or controversial success.

This study has been transitioned to CTIS with ID 2023-507970-42-00 check the CTIS register for the current data.

The purpose of this study is to evaluate the efficacy and safety of
177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care
alone, in adult male patientswith mHSPC.
In this study, the SoC is defined as a combination of Androgen Receptor
Directed Therapy + Androgen Deprivation Therapy.

In this international, open-label, prospective, phase III study, where
approximately 1126 patients with treatment naïve or minimally treated
PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of
Care (SoC) with or without the radioligand 177Lu-PSMA-617. In this study, the
combination for Androgen Receptor Directed Therapy + Androgen Deprivation
Therapy are allowed as SoC.
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.

Intervention with 177Lu-PSMA-11 + standard of care versus standard of care
alone. Crossover form standard of care alone to combination 177Lu-PSMA-11 +
standard of care is possible

Risk: potential side effects of study treatment and GA-PSMA-11 scan
Burden:
The patient will come to the study doctor*s clinic 6 times during the first
cycle (1 cycle is 6 weeks), thereafter 3 times
during each following 5 cycles, thereafter every 12 weeks. After the patient
discontinues study treatment, he/she will be
followed for safety.
See question E4 for all study assessments.