Safety Analyses of the Phase 3 VISION Trial of [Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer.

Background And Objective: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of Lu-PSMA-617 and the impact of longer observation time for patients receiving Lu-PSMA-617 plus SoC.

Methods: VISION was an international, open-label study.

A VISION Substudy of Reader Agreement on Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for Lu-PSMA-617 Radioligand Therapy.

[ Ga]Ga-PSMA-11 ( Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [Lu]Lu-PSMA-617 (Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study.

Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study.

A wide variety of operational issues were encountered with the planning and implementation of an adaptive, dose-finding, seamless phase 2/3 trial for a diabetes therapeutic. Compared with a conventional design, significant upfront planning was required, as well as earlier, more integrated cross-functional coordination. The existing infrastructure necessitated greater flexibility to meet the needs of the adaptive design.

PCR-based ordered genomic libraries: a new approach to drug target identification for Streptococcus pneumoniae.

Described here are the development and validation of a novel approach to identify genes encoding drug targets in Streptococcus pneumoniae. The method relies on the use of an ordered genomic library composed of PCR amplicons that were generated under error-prone conditions so as to introduce random mutations into the DNA. Since some of the mutations occur in drug target-encoding genes and subsequently affect the binding of the drug to its respective cellular target, amplicons containing drug targets can be identified as those producing drug-resistant colonies when transformed into S.