Background: Disease- and tx-related symptoms negatively affect quality of life and may become life-threatening. There is a need for improved understanding, prevention, reduction and mitigation of symptoms, and tools to facilitate remote tracking of pt-reported outcomes (PROs) and support self-management of symptoms. As anticancer txs are increasingly given outside of the clinical settings, DPM tools are becoming more important to support remote symptom management. DPM can improve clinical care and pt outcomes; however, broad adoption requires proven usability and demonstration of real-world clinical utility/impact. ORIGAMA (NCT05694013) is an interventional, open-label, multi-country platform study investigating the clinical utility of DPM tools with specific txs. ORIGAMA will assess atezolizumab (atezo)-specific Roche DPM Modules (F. Hoffmann-La Roche Ltd, Basel, Switzerland; hosted on Kaiku Health DPM platform [Helsinki, Finland]) in two cohorts, to study the impact of DPM on clinical outcomes and healthcare resource utilization, and its feasibility to support at-home tx administration. Methods: Adult pts with ECOG PS of 0–2, an email address, and access to an internet-capable device and internet connection are eligible. In Cohort A, systemic tx-naive pts with metastatic non-small cell lung cancer (NSCLC), extensive-stage SCLC, or Child–Pugh A unresectable hepatocellular carcinoma, with a life expectancy of ≥ 12 weeks (wks) will be randomized 1:1 to a locally approved anticancer regimen of intravenous atezo and local standard-of-care (SoC) support with/without access to the Roche DPM Module. Pts will receive tx until progressive disease or per local SoC. Cohort B will assess the Roche DPM Module in pts receiving 3 cycles of subcutaneous atezo in a hospital setting, followed by 13 cycles of at-home administration by a healthcare professional. Eligible pts have programmed-death ligand 1-positive (expression on ≥ 1% of tumor cells), NSCLC (Stages IIB, IIIA, IIIB [T3–N2]), have completed adjuvant chemotherapy 4–12 wks prior to randomization, and must have a complete resection. Future cohorts may be added to investigate digital health solutions in other tx settings. The primary endpoints are the mean difference in change of the pt-reported Total Symptom Interference Score at Wk 12 from baseline (Cohort A), and flexible care adoption rate at Cycle 6 (Cohort B). The primary analysis for Cohort A will occur when all randomized pts have been followed for ≥ 12 wks and for Cohort B when all pts have completed 16 cycles of tx. Other endpoints include safety and PROs. An exploratory analysis of overall survival will be performed. ~400 pts in Cohort A and 40 pts in Cohort B will be enrolled. Recruitment has started; the first pt to be enrolled in February 2023. Clinical trial information: NCT05694013.