Colorectal cancer (CRC) is the 4th most common cause of new cancer diagnosis and the 2nd leading cause of cancer-related mortality in the United States. Although the clinical outcomes of CRC have recently improved with 5-year relative survival rates of ~65% for all stages combined, advanced or metastatic CRC has a poor prognosis with 5-year OS of ~15%.

CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7- 47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5- 64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pre-treatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and pre-existing anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.

This well written paper examines a cohort of CRC patients for which second line therapy is limited.  By extensive use of biomarkers, a potential way of treating this large group may emerge.

READ THE ARTICLE – https://www.nature.com/articles/s41467-024-45960-2