The combination of anti-PD-1 antibody plus antiangiogenic therapy can play a synergistic antitumor role in the treatment of advanced renal cancer. Shanghai’s toripalimab is a humanized monoclonal antibody against PD-1,which has received a conditional approval in China for the treatment of melanoma in the second line setting, nasopharyngeal carcinoma in the first and third line settings, and urothelial carcinoma in the second line setting. Given that most first line trials in the advanced RCC disease space have not included patients from Asian countries, there exists a considerable unmet need for clinical trials specifically tailored to address the geographical and clinical requirements of this patient population. 

During the ESMO 2023 conference, findings from the Phase III RENOTORCH trial were unveiled, involving 421 patients with unresectable or metastatic clear cell renal cell carcinoma (RCC) who had not received systemic antitumor therapy. The patients were randomly divided into two groups: one receiving toripalimab plus axitinib, and the other receiving sunitinib alone. Both sets of patients continued treatment until disease progression or intolerable side effects occurred. The study's median follow-up period was 14.6 months.

In terms of the primary endpoint, progression-free survival (PFS) assessed through BICR, the combination of toripalimab and axitinib demonstrated significant survival benefits over sunitinib. The median PFS for the experimental group was 18 months, while it was 9.8 months for the control group. Toripalimab plus axitinib consistently outperformed sunitinib across all sub groups. The overall response rate (ORR) was 57% for the toripalimab and axitinib combination, compared to 31% for sunitinib. The duration of response, assessed by BICR, was also notably longer in the experimental arm. Although overall survival (OS) data is still evolving, there is a clear indication of OS benefit with toripalimab and axitinib. However, the OS observed with sunitinib was 26.8 months.

From a safety standpoint, the rate of Grade 3 or higher treatment-emergent adverse events (AEs) was 71.2% for patients on the toripalimab-axitinib combination and 67.1% for those on sunitinib. AEs leading to treatment discontinuation were seen in 14.4% of patients in the toripalimab-axitinib group and 8.1% in the sunitinib group. Fatal AEs were observed in 3.8% and 2.4% of patients, respectively. The primary treatment-related AEs in the toripalimab-axitinib group included hypertension, hypothyroidism, proteinuria, and diarrhea. In the sunitinib group, the common treatment-related AEs were decreased platelet count, decreased white blood cell count, anemia, decreased neutrophil count, and hypertension.

These findings endorse the use of toripalimab combined with axitinib as first-line initial treatment option for advanced RCC.

KOL insights

“We are immensely excited about the RENOTORCH study, a Chinese-led clinical trial conducted in the Chinese population that has demonstrated that combining toripalimab with axitinib can significantly prolong patients’ PFS. We will actively communicate and collaborate with regulatory authorities and hope to soon provide more effective and accessible treatment options to Chinese patients.” – MD, China

Conclusion 

Currently, China’s primary approach towards treating advanced RCC still relies heavily on targeted monotherapy using tyrosine kinase inhibitors (TKIs), however, this approach offers limited benefits to patients. The fact that almost 15% of global kidney cancer-related mortalities occur in China magnifies the significance of this issue. Given the substantial worldwide population of RCC patients residing in China, the results of the RENOTORCH trial are anticipated to transform the approach to advanced RCC treatment on a global scale.

The results presented at the ESMO 2023, showed that the addition of toripalimab to axitinib in the first line treatment setting for advanced RCC patients provides superior clinical outcomes compared to sunitinib. The combination exhibited notably superior progression-free survival (PFS) at 18 months compared to sunitinib, along with a higher overall response rate (ORR).  The combination of toripalimab and axitinib was generally well-tolerated, with a safety profile consistent with each individual agent. 

In July 2023, based on the promising data from the interim analysis of Phase III RENOTORCH trial, China’s National Medical Products Administration (NMPA) has accepted a supplemental new drug application (sNDA) seeking the approval of toripalimab plus axitinib for the treatment of patients with unresectable or metastatic renal cell carcinoma (RCC). The combination has the potential to become a new standard first-line treatment for advanced RCC.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Renal Cell Carcinoma Market Insight And Market Forecast, Renal cell carcinoma Epidemiology Forecast, and Renal Cell Carcinoma Pipeline Insight