Key Points Question What are the diagnostic accuracy and negative predictive value of novel biparametric magnetic resonance imaging (MRI) in biopsy-naive men in detecting and ruling out significant prostate cancer? Findings In this cohort study of 1020 men who underwent both biparametric targeted and standard transrectal ultrasound-guided biopsies, low-suspicion biparametric MRI had a high negative predictive value (97%) in ruling out significant prostate cancer on confirmatory biopsies. Meaning The biparametric MRI used as a triage test in this study was associated with improved prostate cancer risk stratification and may be used to exclude aggressive disease and avoid unnecessary biopsies in 30% of men with clinical suspicion of prostate cancer, although further studies are needed to fully explore this new diagnostic approach.

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The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing of tumor samples and artificial intelligence (AI) allow fast and systematic prediction of tumor neoantigens. This study investigates feasibility, safety, immunity, and anti-tumor potential of the personalized peptide-based neoantigen vaccine, EVX-01, including the novel CD8 + T-cell inducing adjuvant, CAF®09b, in patients with metastatic melanoma (NTC03715985). The AI platform PIONEER TM was used for identification of tumor-derived neoantigens to be included in a peptide-based personalized therapeutic cancer vaccine. EVX-01 immunotherapy consisted of 6 administrations with 5–10 PIONEER TM -predicted neoantigens as synthetic peptides combined with the novel liposome-based Cationic Adjuvant Formulation 09b (CAF®09b) to strengthen T-cell responses. EVX-01 was combined with immune checkpoint inhibitors to augment the activity of EVX-01-induced immune responses. The primary endpoint was safety, exploratory endpoints included feasibility, immunologic and objective responses. This interim analysis reports the results from the first dose-level cohort of five patients. We documented a short vaccine manufacturing time of 48–55 days which enabled the initiation of EVX-01 treatment within 60 days from baseline biopsy. No severe adverse events were observed. EVX-01 elicited long-lasting EVX-01-specific T-cell responses in all patients. Competitive manufacturing time was demonstrated. EVX-01 was shown to be safe and able to elicit immune responses targeting tumor neoantigens with encouraging early indications of a clinical and meaningful antitumor efficacy, warranting further study.