The field of immuno-oncology (IO) has been in need of novel biomarkers ever since 2011. The most promising or anticipated biomarker among high-prescribing physicians in the seven major markets (7MM*) was identified to be measures of tumor mutational burden (TMB), according to GlobalData, a leading data and analytics company.

Sakis Paliouras, PhD, Senior Oncology Analyst at GlobalData, comments: “While IO agents have transformed the treatment of many cancer types, a dearth of biomarkers that could identify the most appropriate patients for treatment persists. This could result in large numbers of patients being unnecessarily exposed to IO therapy side effects, with the hope that they may receive some benefit, when these patients are primarily refractory to IO in the first place.”

Currently, Merck & Co’s Keytruda is the only agent approved in a tumor-agnostic fashion as long as the tumor is of high TMB, as quantified by the FoundationOne CDx companion diagnostic test. Key opinion leaders (KOLs) interviewed by GlobalData point out that the usefulness of such tests is currently only limited to the US, as in other markets reimbursement for the latest diagnostic tests is neither standardized nor swift. Other promising biomarkers ranked were mismatch/homologous repair deficiency, which partly overlaps with TMB, and density of tumor-infiltrating lymphocytes.

Paliouras continues: “In the US, oncology is a protected class, which means that companies can command high prices for new drugs, and payers will have to accept them. The incorporation of biomarkers to restrict eligibility is one of the few options in the payers’ armamentarium to not reimburse high-priced agents if they believe there is no justified patient benefit. Interestingly, this may correlate with the industry’s slow adoption of biomarkers in their prospective clinical trials. That is, there are few, if any, incentives for a company to limit an otherwise large eligible patient population to a smaller, biomarker-restricted one, as this would have obvious implications for the commercial success of new drugs.“

Interestingly, the drug class that would benefit most from predictive biomarkers, immune checkpoint inhibitors (ICIs), is the one that physicians believe is the most challenging to develop biomarkers for.

Paliouras concludes: “There has been extensive criticism by physicians for the lack of prospective analyses of biomarker efficacy in IO clinical trials. Despite this, several companies have invested heavily in omics analyses that delve into correlating measures such as RNA expression, genomic data, or protein data to patient response. GlobalData believes that these datasets will undoubtedly transform the field with time and result in novel biomarkers emerging for IO.”