Companion diagnostics and clinical drug development in oncology: a survey based on US FDA data

Over the past few decades, the drug-diagnostic codevelopment model has gradually transformed oncology drug development. In this model, a predictive biomarker assay, known as a companion diagnostic (CDx), is developed alongside the drug. The incorporation of CDx assays in clinical drug development has facilitated the use of the enrichment trial design, in which patients are selected based on molecular characteristics linked to the drug mechanism of action. In this survey, oncology drugs associated with a CDx assay approved by the FDA until the end of 2025 were investigated, and drug class, clinical trial design, study endpoint, patient population, Orphan Drug status, and expedited review were recorded. During this period, 87 cancer drugs were identified, of which 62 (71%) were indicated for treatment of solid tumors. Kinase inhibitors were the dominant drug class, accounting for 34 drugs (55%). A large proportion of the drugs had obtained Orphan Drug status (63%) and Breakthrough Therapy designation (77%). The average patient population sufficient to obtain FDA approval was 279, with 16 (26%) drugs approved based on fewer than 100 patients, often supported by single-arm, open-label clinical trials. For 49 (79%) of the drugs, efficacy documentation was generated based on one single clinical trial. The primary endpoint in these trials was most often objective response rate and progression-free survival. When evaluating the enrichment trial design, the number of patients required to demonstrate clinical efficacy and obtain FDA approval is low compared to the traditional all-comers design, which means that safety evaluation could be compromised.