Dr Zhang on the Rationale for Investigating Sintilimab/Axitinib in FH-Deficient RCC

Xingming Zhang, MD, medical oncologist, West China Hospital, discusses the rationale for investigating the combination of sintilimab and axitinib (Inlyta) in patients with advanced fumarate hydratase (FH)–deficient renal cell carcinoma (RCC) in a phase 2 trial (NCT04387500).

Findings from the ongoing trial presented at the 2023 American Urological Association Annual Meeting showed that evaluable patients treated with the combination achieved an overall response rate of 65.2%, including a complete response rate of 13% and a partial response rate of 52.5%. The rates of stable disease and progressive disease were 21.7% and 13%, respectively, and the disease control rate was 87%. The average tumor shrinkage rate was 48%.

RCC is a heterogeneous tumor type, and each subtype is defined by distinct histological features, clinical manifestations, and responses to treatment, Zhang begins. Previously, non–clear cell FH-deficient RCC was categorized as a type 2 papillary RCC; however, it was later reclassified into its own subtype because of its unique characteristics, Zhang explains.

Several studies have explored therapeutic targets in FH-deficient RCC, Zhang notes. However, agents directed at these targets have not generated efficacy in these patients, and no standard treatment strategy currently exists for patients with FH-deficient RCC, he adds.

FH-deficient RCC is charactered by a high infiltration of immune cells with a high expression of PD-L1, he continues.

Although primary tumors in this subset of patients are immune-hot, metastases have a further activated tumor immune microenvironment, Zhang adds. These factors prompted investigators to explore dual checkpoint inhibition with sintilimab plus axitinib for this patient population, Zhang concludes.