EXoPERT EMERALD Clinical Study

EXoPERT EMERALD: Early Multi-cancer Study of EV's Ramen-AL Linked Diagnosis Clinical Study Protocol

The purpose of this study is to establish a multi-center clinical repository of blood samples to support the development and evaluation of an artificial intelligence-based in vitro diagnostic software. The software analyzes surface-enhanced Raman spectroscopy (SERS) profiles of extracellular vesicles (EVs) extracted from human plasma for the early detection of multiple cancers, including lung, ovarian, breast, pancreatic, and colorectal cancers.

The EMERALD study is a multi-center study (Protocol No. EXPT-MC-F-2024) designed to establish a clinical plasma repository for the training and clinical evaluation of the ExoPred deep learning software

The study protocol operates in three sequential phases to ensure data integrity and prevent algorithmic overfitting:

Phase 1 (Algorithm Training Stage): A minimum of 500 samples are analyzed to develop the algorithm and establish the initial clinical cut-off values, followed by a database lock.

Phase 2 (Algorithm Lock-Readiness Assessment): A minimum of 50 newly acquired unknown samples are evaluated to assess model robustness before the final algorithm is formally locked in the Technical File.

Phase 3 (Blinded Independent Stage): A minimum of 200 independent samples, strictly excluded from prior phases, are tested under strict blinding to evaluate finalized clinical sensitivity, specificity, and accuracy.

The locked software analyzes surface-enhanced Raman spectroscopy (SERS) profiles of extracellular vesicles (EVs) to detect five target malignancies: lung, breast, colorectal, pancreatic, and ovarian cancers. Based on multi-class classification probability scoring, the predicted tissue of origin (TOO) can be presented for up to a maximum of three cancer types. All data handling and automated quality checks follow standard operating procedures (SOPs) within a 21 CFR Part 11 compliant EDC system.

Inclusion Criteria:

• Subject aged 45 years or older with a biopsy-proven or clinically suspected primary lung, breast, colorectal, pancreatic, or ovarian cancer, based on objective findings such as radiological, serological, endoscopic, or cytological findings, whose blood was collected prior to any systemic or definitive therapy for the cancer.
• Subjects who are willing and able to provide written informed consent.
• Subjects who are willing and able to comply with the study requirements.

Exclusion Criteria:

• Any history of cancer diagnosed and treated within 5 years prior to the date of consent.
• Subjects with a history of previous cancer treatment via surgical resection, hormonal cancer treatment, chemotherapy, radiotherapy within the past 6 months for recent cancer diagnosis.
• Subjects who have any history of an allogeneic bone marrow, stem cell transplant, or solid organ transplant.
• Subjects who are pregnant or breastfeeding women.
• Subjects who have consented and have undergone treatment in any other cancer related clinical trials withinthe past 6 months.
• Subjects who are currently in active treatment for drug abuse.
• Subjects who have received any treatment related to lung, breast, colorectal, pancreatic, or ovarian nodules, such as hormones prior to entering the study.
• Unsuitable sample for testing due to contamination, hemolysis, etc.