SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.
Prostate cancer is the most commonly diagnosed cancer in North American men; however, prognosis is relatively good given early diagnosis. This motivates the need for fast and reliable prostate cancer sensing. Diffusion weighted imaging (DWI) has gained traction in recent years as a fast non-invasive approach to cancer sensing. The most commonly used DWI sensing modality currently is apparent diffusion coefficient (ADC) imaging, with the recently introduced computed high-b value diffusion weighted imaging (CHB-DWI) showing considerable promise for cancer sensing. In this study, we investigate the efficacy of ADC and CHB-DWI sensing modalities when applied to zone-level prostate cancer sensing by introducing several radiomics driven zone-level prostate cancer sensing strategies geared around hand-engineered radiomic sequences from DWI sensing (which we term as Zone-X sensing strategies). Furthermore, we also propose Zone-DR, a discovery radiomics approach based on zone-level deep radiomic sequencer discovery that discover radiomic sequences directly for radiomics driven sensing. Experimental results using 12,466 pathology-verified zones obtained through the different DWI sensing modalities of 101 patients showed that: (i) the introduced Zone-X and Zone-DR radiomics driven sensing strategies significantly outperformed the traditional clinical heuristics driven strategy in terms of AUC, (ii) the introduced Zone-DR and Zone-SVM strategies achieved the highest sensitivity and specificity, respectively for ADC amongst the tested radiomics driven strategies, (iii) the introduced Zone-DR and Zone-LR strategies achieved the highest sensitivities for CHB-DWI amongst the tested radiomics driven strategies, and (iv) the introduced Zone-DR, Zone-LR, and Zone-SVM strategies achieved the highest specificities for CHB-DWI amongst the tested radiomics driven strategies. Furthermore, the results showed that the trade-off between sensitivity and specificity can be optimized based on the particular clinical scenario we wish to employ radiomic driven DWI prostate cancer sensing strategies for, such as clinical screening versus surgical planning. Finally, we investigate the critical regions within sensing data that led to a given radiomic sequence generated by a Zone-DR sequencer using an explainability method to get a deeper understanding on the biomarkers important for zone-level cancer sensing.
CF33-hNIS-anti-PD-L1 is an oncolytic chimeric poxvirus encoding two transgenes: human sodium iodide symporter and a single-chain variable fragment against PD-L1. Comprehensive preclinical pharmacology studies encompassing primary and secondary pharmacodynamics and biodistribution and safety studies were performed to support the clinical development of CF33-hNIS-anti-PD-L1. Most of the studies were performed in triple-negative breast cancer (TNBC) models, as the phase I trial is planned for patients with TNBC. Biological functions of virus-encoded transgenes were confirmed, and the virus demonstrated anti-tumor efficacy against TNBC models in mice. In a good laboratory practice (GLP) toxicology study, the virus did not produce any observable adverse effects in mice, suggesting that the doses proposed for the clinical trial should be well tolerated in patients. Furthermore, no neurotoxic effects in mice were seen following intracranial injection of the virus. Also, the risk for horizontal transmission of CF33-hNIS-anti-PD-L1 was assessed in mice, and our results suggest that the virus is unlikely to transmit from infected patients to healthy individuals. Finally, the in-use stability and compatibility of CF33-hNIS-anti-PD-L1 tested under different conditions mimicking the clinical scenarios confirmed the suitability of the virus in clinical settings. The results of these preclinical studies support the use of CF33-hNIS-anti-PD-L1 in a first-in-human trial in patients with TNBC.
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