Abstract IA16: Trial enrichment and proof of concept studies

Identification of oncogene addiction loops has provided new therapeutic targets in oncology. Selective targeting of the ABL-BCR fusion in patients with chronic lymphocytic leukemia using imatinib was a major clinical breakthrough. Similar approaches in other solid tumors led to the approval of additional biomarker-driver molecular therapies (e.g., vemurafenib in BRAF mutated melanoma). Success of this approach was contingent on the identification of biomarkers that could help identify patients most likely to respond to these therapies. This spurred efforts to implement clinical trials able to detect efficacy in specific patient populations, specifically those enriched in the biomarker under evaluation. This has also been applied in hepatocellular carcinoma with mixed results. Approval of ramucirumab in patient with elevated AFP is the first example of successful trial enrichment, while tivantinib is paradigmatic of a negative biomarker enrichment trial. Lack of recurrent druggable mutations makes biomarker-driven clinical trials in HCC more difficult, which underscores the need for predictive biomarkers of immune therapies.

Citation Format: Augusto Villanueva-Rodriguez. Trial enrichment and proof of concept studies [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA16.