Dr Xu on Ongoing Biomarker Research in Metastatic RCC

Wenxin (Vincent) Xu, MD, physician, Dana-Farber Cancer Institute, and assistant professor of medicine, Harvard Medical School, discusses ongoing efforts to identify emerging biomarkers in metastatic renal cell carcinoma (RCC).

The ongoing phase 2 OPTIC RCC trial (NCT05361720) is assessing the use of established biologic clusters to guide selection between an immuno-oncology (IO) and TKI approach vs an IO/IO regimen for patients with clear cell RCC, Xu begins. The study utilizes mRNA gene expression signatures derived from prior phase 3 trials like IMmotion151 (NCT02420821) and JAVELIN Renal 101 (NCT02684006), he notes. RNA sequencing will be performed on metastatic tissue samples from newly diagnosed patients with RCC and used to assign tumor clusters. This classification informs treatment selection, as patients with angiogenic clusters will receive a combination of cabozantinib (Cabometyx) and nivolumab (Opdivo), while those with immune inflammatory clusters are treated with ipilimumab (Yervoy) and nivolumab.

Patients are eligible for enrollment on the study if they have not been previously exposed to systemic therapy, including in the neoadjuvant or adjuvant setting, and have at least 1 measurable lesion as defined by RECIST v1.1 criteria. The primary end point of the OPTIC RCC trial is objective response rate. Study investigators hypothesize that using these molecular tumor clusters to guide first-line therapy will result in a 20% higher ORR compared to historical controls from previous unselected trials.

Although OPTIC RCC is a small trial, it represents a shift towards personalized medicine in RCC, Xu states. By leveraging gene expression profiles, OPTIC RCC seeks to identify specific biomarkers that predict response to targeted therapies versus immunotherapies, thereby optimizing treatment decision-making in RCC, Xu adds.

In parallel with the OPTIC RCC trial, there are ongoing efforts across different research groups to investigate circulating biomarkers that could serve as predictors of therapy response, Xu continues. These efforts aim to develop blood-based tests that could streamline treatment selection and monitoring, he explains.

Overall, these initiatives reflect a growing emphasis on biomarker-driven approaches in oncology, offering hope for more tailored and effective treatments for patients with RCC and other cancers, Xu concludes.