Standard of Care +/- 177Lu-PSMA-617 In de Novo mHSPC Patients With Poor PSA Response (PEACE6-Poor Responders)

Inclusion Criteria27

• All of the following criteria must be met ahead of randomization to satisfy trial eligibility requirements:
• Signed a written informed consent form prior to any trial specific procedures.
• Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients.
• Aged ≥18 years old
• Life expectancy \> 6 months as per investigator estimate
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Men with histologically or cytologically confirmed adenocarcinoma of the prostate
• De novo metastatic disease defined by clinical or radiographic evidence of metastases at diagnosis (i.e. before any treatment started). If not available, a more recent imaging can be used
• Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful bone metastases are not eligible
• A pre-randomization 68Ga-PSMA-11 PET/CT scan performed within 4 weeks prior to randomization in the trial.
• FDG PET scan is not required for this protocol. All patients will be treated independently from the results of pre-randomization PSMA PET scan: patients with PSMA-positive or PSMA-negative disease according to PROMISE 2.0 criteria are eligible.
• Have 6 to 8 months of previous AND ongoing standard systemic treatment for prostate cancer consisting in either:
• ADT with an androgen receptor signaling inhibitor (ARSI) (i.e., abiraterone (plus prednisone), or apalutamide or enzalutamide) ± radiotherapy \*\*
• ADT with docetaxel\* plus an ARSI (i.e. abiraterone (plus prednisone), or darolutamide,) ± radiotherapy\*\*
• Note:
• \*Docetaxel must have been stopped at least 4 weeks ahead of randomization.
• \*\* Previous radiotherapy to the primary tumor and/or to the metastases is accepted as long as it was not PSMA-based and must has been completed at least 4 weeks ahead of randomization.
• Stable or declining PSA level but not a rising one
• Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation
• Testosterone level \< 50 ng/dl or \< 1.7 nmol/L
• Be fit enough for 177Lu-vipivotide tetraxetan treatment:
• Adequate bone marrow function: hemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization), absolute neutrophil count ≥1.5 x10⁹/L, platelet count \>100 x10⁹/L
• Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0 x upper limit of normal (ULN), or ≤ 5.0 x ULN in the presence of liver metastases; bilirubin \<1.5 x ULN (unless known or suspected Gilbert syndrome, then \<3 x ULN is permitted)
• Adequate renal function: calculated creatinine clearance ≥ 50 ml/min (using the MDRD or CKD EPI method).
• For sexually active men with female partners of reproductive potential or with pregnant women, agreement to use a condom with another effective contraceptive method during trial participation and up to 14 weeks after study treatment completion.
• Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
• Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.