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.

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Xingming Zhang, MD, discusses the rationale for investigating the combination of sintilimab and axitinib in patients with advanced fumarate hydratase-deficient renal cell carcinoma in a phase 2 trial.


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

Xingming Zhang, West China Hospital, discusses efficacy, safety, and quality of life (QOL) findings from a phase 2 trial (NCT04387500) investigating the combination of sintilimab and axitinib (Inlyta) in patients with fumarate hydratase (FH)–deficient renal cell carcinoma (RCC).

This ongoing phase 2 trial aims to enroll 41 patients who are 18 years of age and older and who have FH-deficient RCC across 8 sites in China. Eligibility criteria include confirmed germline and/or somatic FH large deletions and/or alterations, an ECOG performance score of 2 or lower, and an expected survival of more than 3 months. As of April 2023, the efficacy-evaluable population consisted of 23 patients, and 36 patients were evaluable for safety and quality of life. Patients received 200 mg of sintilimab injection every 3 weeks plus 5 mg of oral axitinib twice a day.

Sintilimab plus axitinib produced an overall response rate of 65.2%, with 13%, 52.5%, 21.7%, and 13% of patients achieving best responses of complete response, partial response, stable disease, and progressive disease, respectively. The average rate of tumor shrinkage was 48%, and the combination elicited a disease control rate of 87%.

Regarding safety, all patients experienced adverse effects (AEs) of any grade, and 25% of patients had grade 3 or higher AEs. The most common AEs included proteinuria, hypertriglyceridemia, increased blood creatinine levels, hypothyroidism, increased adrenocorticotropic hormone levels, and hypothyroidism.

This trial is also evaluating patient-reported outcomes using the Functional Assessment of Cancer Therapy – kidney symptom index-19 (FKSI-19) and the visual analogue scale (VAS), Zhang says. The mean FKSI-19 total score was stable after treatment with sintilimab plus axitinib, with a slight increase after 6 months of treatment. The mean VAS score was also stable after treatment.

The combination of sintilimab and axitinib had a manageable safety profile and generated promising tumor responses in patients with FH-deficient RCC, Zhang concludes.

Xingming Zhang discusses efficacy, safety, and quality of life findings from a phase 2 trial investigating the combination of sintilimab and axitinib in patients with fumarate hydratase–deficient renal cell carcinoma.

Xingming Zhang

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

Dr Zhang on Sintilimab Plus Axitinib in FH-Deficient RCC