[18F]Fluorthanatrace - Positron Emission Tomography (FTT-PET) and ctDNA to Predict Response to PARP Inhibitor Therapy in Metastatic Prostate Cancer (mPC)

Prediction performance of FTT-PET as measured by concordance index (C-index)

Prediction performance of FTT-PET in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is mathematically calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

Time frame: At baseline prior to PARPi therapy and post cycle 1 (estimated total time 28 days)

Prediction performance of FTT-PET as measured by area under the receiver operating characteristic (ROC) curve

Prediction performance of FTT-PET in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy and post cycle 1 (estimated total time 28 days)

Prediction performance of EnhanceAR-Seq ctDNAas measured by concordance index (C-index)

Prediction performance of EnhanceAR-Seq ctDNA analysis in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Prediction performance of EnhanceAR-Seq ctDNA as measured by area under the receiver operating characteristic (ROC) curve

Prediction performance of EnhanceAR-Seq ctDNA analysis in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA collectively as measured by concordance index (C-index)

Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA analysis collectively in predicting participant response to PARPi therapy will be assessed by concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), and at progression if applicable (estimated total time 6 months)

Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA collectively as measured by area under the receiver operating characteristic (ROC) curve

Prediction performance of FTT-PET and EnhanceAR-Seq ctDNA analysis collectively in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), and at progression if applicable (estimated total time 6 months)

Sensitivity of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

Sensitivity is calculated as the proportion of true positives divided by the sum of true positives and false negatives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate sensitivity. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Specificity of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

Specificity is calculated as the proportion of true negatives divided by the sum of true negatives and false positives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate specificity. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes the performance of model. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Positive predictive value (PPV) of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

PPV is calculated as the number of true positives divided by the sum of the number of true positives and number of false positives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate PPV. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Negative predictive value (NPV) of EnhanceAR-Seq ctDNA in identifying mPC patients who respond to PARPi therapy

NPV is calculated as the number of true negatives divided by the sum of the number of true negatives and number of false negatives. The area under the Receiver Operating Characteristic (ROC) curve will be calculated to identify the optimal cutpoint on the ROC corresponding to the maximized Youden index to evaluate NPV. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Predictive performance improvement as measured by change in concordance index of FTT-PET and EnhanceAR-seq ctDNA compared to only FTT-PET or only EnhanceAR-seq ctDNA

Prediction performance of FTT-PET and EnhanceAR-seq ctDNA in predicting participant response to PARPi therapy will be assessed by the concordance index (C-index). The C-index is calculated as the number of concordant pairs divided by the number of comparable pairs. A C-index of 1 indicates perfect ranking, values close to 0.5 indicate random prediction, and values between 0.5 and 1 suggest some predictive ability prediction (a value below 0.5 can be reversed by switching the response's 0 and 1 labels).

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)

Predictive performance improvement as measured by area under the receiver operating characteristic (ROC) curve of FTT-PET and EnhanceAR-seq ctDNA compared to only FTT-PET or only EnhanceAR-seq ctDNA

Prediction performance of FTT-PET and EnhanceAR-seq ctDNA in predicting participant response to PARPi therapy will be assessed by the area under the ROC curve. The ROC curve is a graphical plot that illustrates the performance of a model at various threshold settings and the area under the curve (AUC) is a single scalar value between 0 and 1 that summarizes model performance. A higher AUC value indicates better performance.

Time frame: At baseline prior to PARPi therapy, post cycle 1 (cycle is an estimated 28 days), 12 weeks after start of PARPi therapy, and at progression if applicable (estimated total time 6 months)