Functional precision medicine for chemotherapy-refractory metastatic colorectal cancer: the randomized DSEE-CRC trial

The clinical benefit of approved later-line therapies in metastatic colorectal cancer (CRC) is limited following failure of oxaliplatin- and irinotecan-based chemotherapy with additional biological agents selected according to tumor mutational status. The DSEE-CRC trial randomizes patients with chemotherapy-refractory metastatic CRC to therapies informed by functional precision cancer medicine (PCM) using patient-derived tumoroids (PDTs) or to the standard third-line regimen of trifluridine-tipiracil/bevacizumab. Eligible patients have failed first-line standard chemotherapy for unresectable, measurable metastases in the liver, peritoneum, or superficial lymph nodes and have at least one biopsy-accessible lesion. PDTs are established from a fresh biopsy specimen and exposed to more than 20 anti-cancer drugs, producing an in-vitro diagnostic report that summarizes and ranks PDT drug sensitivity. After second-line chemotherapy failure, patients are randomized (2:1) to receive either investigational therapy guided by the PDT report or trifluridine-tipiracil/bevacizumab. The primary objective is to evaluate the diagnostic performance of the PDT-guided approach. Clinical endpoints include disease control rates at prespecified intervals until treatment failure, progression-free and overall survival, and safety. The trial also assesses relevant quality-of-life domains and the cost-effectiveness of PDT-informed therapy. The DSEE-CRC trial addresses efficacy and safety of PCM in late-stage CRC while also highlighting the regulatory challenges of simultaneously investigating medicinal products and a new in-vitro diagnostic device for precision oncology. NCT07171554, registered 12 September 2025.