Several updates based on feedback from the US FDA. Update: studies evaluating 68Ga-PSMA-11 PET or 18F-DCFPyL-PSMA PET in the Study Rationale, including addition of point estimate ranges for the studies quoted. Clarify: study rationale that the study was to be performed in patients eligible for curative intent, locoregional therapy. Clarify: baseline conventional imaging was required if not performed in the 60 days prior to screening. Clarify: assessment of objectives and endpoints was based on central BIE. Add: exploratory objective added to “evaluate the number of PET-positive pelvic LNs by central BIE as compared to the number of pathologic positive LNs (by local histopathology analysis) in each region”, with corresponding endpoint. Clarifiy: dose of IMP could be 8 mCi (296 MBq) ± 20% rhPSMA-7.3 (18F). Add: to allow discussion of rhPSMA-7.3 (18F) PET results and further procedures/treatment plan to be conducted by telephone at the clinician’s discretion. Clarify: physical examination would be focused in nature. Clarify: safety follow-up visit was to be conducted within 1 to 3 days post-IMP administration. Add: interim look at the percentage of pN1 and pN0 patients after enrollment of 150 patients. Amend: inclusion criterion 4 to remove primary treatment with EBRT. Clarify: additions to standard of care surgical treatments for patients with M0 and M1 disease on local PET interpretation. Clarify: added to confirmatory imaging when used as SoT. Define: unrelated AE updated. Update: sample size and number of evaluable patients required before enrollment will stop, plus the number of positive and negative cases required for enrollment to stop. Update: analysis sets. Clarify: rhPSMA-7.3 (18F) would be considered effective in detecting N1 disease if the co-primary endpoints were met by the same 2 of 3 readers. Other minor typographical edits and clarifications.

Germany specific Several updates to implement feedback from BfArM: Add: text on the replacement of patients who dropout. Exclusion criterion added for patients with known hypersensitivity to the active substance or any excipients of the IMP.

Patient safety and BfArM feedbackfeedback (COVID-19): Add: latest NCCN Guidelines. Combine: exploratory objectives/endpoints 2 & 3. Extend: screening: 28-45 days (COVID-19). Add: Visits 1 and 2 combined option, screening evaluation could occur on day of rhPSMA-7.3 (18F) administration (COVID-19) and clarify that the procedure was to combine IMP manufacture visits. Extend: safety follow-up visit to within 1-5 days (COVID-19). Extend: period from Visit 2 to the scheduled surgery and/or follow up procedures up to 60 (COVID-19). Clarify: study population to be treatment naïve and receive standard of care and clarifications added to inclusion criteria risk definitions. Add: exclusion criterion for patients with hypersensitivity to active substance or any IMP excipient. Add: baseline conventional imaging to be performed at least 24 hours prior to the investigational rhPSMA-7.3 (18F) PET scan. Add: focused physical examination could be performed by a clinician and could be by telephone. Specify: when collected, pre-sacral LNs to be placed in a separate packet from other specimens prior to pathology assessment. Increase: from 2-3 central readers for the rhPSMA-7.3 (18F) PET scans and the information they were provided add: Independent Review Charter. Clarify: conventional imaging performed at non-participating institutions allowed if scans were reviewed by study site. Add: text on replacement of dropouts. Amend: time from end of injection of rhPSMA-7 (18F) to imaging start from 50-90 mins to 50-70 mins. Update: SAE reporting email address and clarify SAEs to be reported immediately. Add: criteria to temporarily halt/stop enrollment. Add: exclude patients with known hypersensitivity to the active substance or any IMP excipient. Add: option for remote study monitoring (COVID-19). Clarify: urgent safety measures may include amendments made due to the COVID-19 pandemic to ensure patient safety by minimizing SARS-CoV-2 exposure. Minor typographical edit.

Updates to implement feedback from BfArM: Remove: reference to remote consent and pre-screening via telephone contact, which were not permitted in Germany. Administrative change to update the Medical Monitor details.