A groundbreaking phase 2 clinical trial has revealed promising results for a new combination therapy in treating a rare and aggressive form of kidney cancer, offering hope for patients with limited treatment options.
Researchers from Renji Hospital, Shanghai Jiao Ton University School of Medicine, have demonstrated that the combination of lenvatinib (Lenvima) and tislelizumab (Tevimbra) achieved an impressive 93.3% objective response rate in patients with fumarate hydratase-deficient renal cell carcinoma (FH-RCC).
Unprecedented Response Rates
The preliminary data, presented by Dr. Wen Kong at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), showed that among 15 evaluable patients, three achieved complete response (20.0%). The median time to response was notably quick at just 6 weeks, with neither progression-free survival nor overall survival reached at the time of analysis.
Study Design and Patient Population
The single-center, single-arm phase 2 trial enrolled 17 patients between September 2023 and October 2024. Participants received daily oral lenvatinib (20 mg) combined with intravenous tislelizumab (200 mg) administered every three weeks. The study population reflected the typical FH-RCC demographic, with a median age of 37 years (range 24-61), and included 14 male and 3 female patients.
Safety and Tolerability
The safety profile appeared manageable, though requiring careful monitoring. While 94.1% of patients experienced adverse events of any grade, only 23.5% developed grade 3 or higher events. Dose modifications were necessary in 47.1% of patients, highlighting the importance of careful patient monitoring and management.
Understanding FH-RCC
FH-RCC represents a particularly challenging form of kidney cancer, primarily affecting young adults. The disease is characterized by germline mutations in the FH gene, which leads to fumarate accumulation and subsequent activation of hypoxia-inducible factor (HIF). This activation triggers tumor growth through multiple pathways, including VEGF and EGFR signaling.
Mechanism of Action
The combination therapy's success may be attributed to its dual-targeting approach. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, blocks blood vessel formation by inhibiting VEGF receptors. Tislelizumab, a PD-1 inhibitor, complements this action by enhancing the immune system's ability to recognize and attack cancer cells.
Clinical Implications
This new therapeutic approach could represent a significant advancement over existing treatment options. The current National Comprehensive Cancer Network guidelines recommend a combination of bevacizumab and erlotinib, based on decade-old data. Dr. Kong emphasized that the treatment landscape for RCC has evolved substantially, necessitating new approaches that incorporate modern immunotherapy and targeted agents.
While these results are preliminary and based on a small patient population, they suggest that the lenvatinib-tislelizumab combination could become a valuable first-line treatment option for patients with FH-RCC. Continued follow-up and larger studies will be crucial to confirm these encouraging findings.
