Personalized vs. Fixed-Activity 177Lu-PSMA-617 Radiopharmaceutical Therapy (PRODIGY-2)

Best biochemical response

Maximum percent decrease of serum prostate-specific antigen (PSA) after first administration.

Time frame: From first administration until 52 weeks or the start of another anti-cancer treatment or death, whichever is earliest

PSA progression-free survival (PSA-PFS)

Time from first administration to an increase in PSA greater than 25%, and greater than 2 ng/ml, above nadir, confirmed at least 3 weeks later.

Time frame: From date of first administration until the date of PSA progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months

Best radiological response rates

Percentage of participants achieving each RECIST 1.1 response category as their best response: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response (i.e., CR or PR; a.k.a. overall response rate, ORR), disease control (i.e CR, PR or SD; a.k.a. disease control rate, DCR).

Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)

Radiological progression-free survival (rPFS)

Time from first administration to the date of radiographic disease progression based on RECIST 1.1/PCWG3.

Time frame: From date of first administration until the date of radiological progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months

Investigator-assessed overall PFS

Time from first administration to the earliest of clinical (worsening of a patient's clinical status attributed to disease progression), biochemical or radiological progression considering all data (scheduled and unscheduled) available to the investigator.

Time frame: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months

Time to first symptomatic skeletal event (SSE)

Time to first Symptomatic Skeletal Event (SSE) is defined as the time from first administration to the date of the SSE. The SSE date is the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurred first.

Time frame: From date of first administration until the date of first SSE or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months

Overall survival (OS)

Overall Survival (OS) is defined as the time from the date of the first administration to the date of death due to any cause.

Time frame: From date of first administration until the date of death, assessed over a minimum of 60 months

Metabolic response on FDG-PET/CT

Metabolic response is defined as complete metabolic response (CMR, disappearance of all lesions on FDG PET), partial metabolic response (PMR, decrease of uptake by ≥30%), stable metabolic disease (SMD, variation of FDG uptake by \<30%), progressive metabolic disease (PMD, increase of FDG uptake by ≥30%)

Time frame: At baseline and at 12 weeks

Molecular response on PSMA-PET/CT

Molecular response is defined as the variation of molecular tumor volume (MTV) on PSMA-PET/CT

Time frame: At baseline and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

Best molecular response on quantitative 177Lu SPECT/CT during treatment

Best molecular response is defined as the maximum percent decrease of molecular tumor volume (MTV) at any time after post-treatment quantitative 177Lu SPECT/CT performed on the first cycle's Day 3, up to the post-treatment quantitative 177Lu SPECT/CT performed on the last cycle's Day 3

Time frame: From first cycle's Day 3 until the last cycle's Day 3 (each cycle is 6 weeks, up to 6 consecutive cycles)

Number of participants with any adverse events (AEs)

All adverse events that occur from the first administration of 177Lu-PSMA-617 until 6 weeks after the last administration of 177Lu-PSMA-617 or prior to the initiation of subsequent anticancer treatment.

Time frame: From first administration to the end of treatment (each cycle is 6 weeks, up to 6 cycles)

Number of participants with laboratory adverse events (AEs)

Adverse events seen on laboratory (hematology, biochemistry) that occur from the first administration of 177Lu-PSMA-617 until progression or until the initiation of subsequent anticancer treatment if earlier.

Time frame: From date of first administration until the date of investigator-assessed progression or of the start of another anti-cancer treatment or of death, whichever came first, assessed over a minimum of 60 months

Number of participants with delayed adverse events of special interest (AESIs)

Delayed AESIs (renal impairment and secondary hematological malignancies) that occur from the first administration of 177Lu-PSMA-617 until death (or study termination)

Time frame: From date of first administration until the date of death, assessed over a minimum of 60 months

Variation of score on EuroQol-5 Dimension-5 Level (EQ-5D-5L) questionnaire at baseline

Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

Variation of score on Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire at baseline

Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

Variation of score on Brief Pain Inventory (BPI-SF) questionnaire at baseline

Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)

Variation of score on Multidisciplinary Salivary Gland Society (MSGS) questionnaire at baseline

Time frame: At baseline, at 18 weeks, and at the end of treatment (each cycle is 6 weeks, up to 6 consecutive cycles)