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Advances within molecular diagnostics have enabled us to identify a number of oncogenic drivers across different cancers. Many cancers can now be divided into subgroups based on molecular characteristics, and an increasing number of targeted anticancer drugs have been developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. With the recent approval of entrectinib, larotrectinib, and pembrolizumab for site-agnostic indications, biomarker-guided drug development has entered into a new phase. The review focuses on the general principles of drug-diagnostic codevelopment, especially basket trials and site-agnostic drug development. Special attention is paid to entrectinib, larotrectinib, and pembrolizumab. The recent approval of entrectinib, larotrectinib, and pembrolizumab must be regarded as a paradigm shift in biomarker-guided oncology drug development. For a site-agnostic indication, it is important to have in mind the central role of the companion diagnostic (CDx), as the assay defines the 'disease' and the patient population to be treated. A number of site-agnostic drugs are currently in development and here, it is important that CDx assay development is given high priority, so an analytical and clinical validated assay is available at the time of drug approval. [ABSTRACT FROM AUTHOR]

The immune checkpoint inhibitors pembrolizumab and nivolumab together with their diagnostic assays have recently been granted market authorization for treatment of advanced non-small-cell lung cancer in the USA. The two assays, PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx (both by Dako, Glostrup, Denmark), are the first PD-L1 IHC assays to obtain regulatory approval through the Premarket Approval process. This approval is supported by recent clinical studies that have shown a positive correlation between PD-L1 expression and the outcome following treatment with different PD-1/PD-L1 checkpoint inhibitors. These diagnostic assays are able to identify the group of non-small-cell lung cancer patients who will benefit most from treatment with the immune checkpoint inhibitors. However, so far, it is only the PD-L1 IHC 22C3 pharmDx assay, which is linked to the use of pembrolizumab, that has obtained regulatory status as a companion diagnostic. [ABSTRACT FROM PUBLISHER]