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Standard of care (SoC) for eligible patients with unresectable Stage III non-small cell lung cancer (NSCLC) is the PACIFIC regimen, chemoradiotherapy (CRT) followed by durvalumab, with pneumonitis being the most common adverse event leading to treatment discontinuation. ON TRAX was a multicenter, prospective pilot study that evaluated the ability of a multiparametric remote monitoring system to detect early signs of pneumonitis in patients receiving durvalumab. The pilot aimed to enroll 75 patients (from 25 sites) with unresectable stage III NSCLC after CRT, but prior to receiving SoC durvalumab, with no major comorbidities and not on oxygen. Patients were monitored remotely while on durvalumab for up to one year with a platform of mobile devices (FDA-cleared wearable recording continuous SpO2, respiratory rate, pulse, temperature and motion; spirometer for daily lung function; tablet for patient reported outcomes) and digital applications. The primary objective of the study was to identify pneumonitis by grade, with an exploratory objective to develop a longitudinal algorithm that predicts pneumonitis early. After all the data was collected, individual daily pneumonitis risk scores between 0-1 were computed retrospectively using a pre-monitoring baseline score based on established risk factors plus a weighted sum of univariate vital sign and spirometry variables with thresholds optimized based on clinician-confirmed pneumonitis cases. A rolling pneumonitis risk score was calculated by taking the average of daily scores over the prior five days. We used a k-fold (k=3) approach for the training data set and held an additional 20% of the total data points for validation. The pilot was terminated prematurely due to low enrollment during COVID-19 pandemic and low patient retention for the length of the study. Of the 40 enrolled patients (median age 65 years, 60% male, 60% stage IIIA), nine (23%) completed the study and 31 discontinued early (48% due to study closure, 23% withdrawal of consent, 5% device-related AEs), but remained on SoC durvalumab. Median (IQR) length of monitoring was 81 (44-206) days with a total of 76,960 hours of data. Only four patients (10%) experienced pneumonitis while on the study, with three recorded as grade 2 and 1 as grade 3. The best predictive performance of the longitudinal algorithm was observed with the rolling pneumonitis risk score. Setting a threshold of >0.68 for the score yielded 75% sensitivity, 65% specificity and an odds ratio of 5.5 [95% CI: 0.54-58.8] for correctly predicting pneumonitis within two weeks prior to diagnosis. Even with low incidence of on-study pneumonitis, the longitudinal algorithm developed using remote monitoring demonstrated potential in predicting pneumonitis in patients receiving durvalumab post-CRT when their rolling pneumonitis risk score exceeded the threshold. Future research with a larger sample size and longer follow-up is needed for the validation and refinement of the algorithm. [ABSTRACT FROM AUTHOR]