Toripalimab Plus Axitinib Approved in China for Frontline Renal Cell Carcinoma

The National Medical Products Administration of China has approved toripalimab combined with axitinib (Inlyta) for use in the first-line treatment of patients with medium- to high-risk unresectable or metastatic renal cell carcinoma (RCC).¹

The regulatory decision was supported by data from the phase 3 RENOTORCH study (NCT04394975) in which the doublet (n = 210) significantly improved blinded independent central review (BICR)–assessed progression-free survival (PFS) vs sunitinib (Sutent) monotherapy (n = 211), at a median of 18.0 months (95% CI, 15.0-not evaluable [NE]) and 9.8 months (95% CI, 8.3-13.8), respectively (stratified, HR; 0.65; 95% CI, 0.49-0.86; P = .0028).2 The 12-month PFS rates with the doublet and the monotherapy were 62.7% and 45.4%, respectively; at 24 months, these rates were 44.6% and 30.2%, respectively.

“From a global perspective, targeted therapy in combination with immunotherapy has become the standard treatment approach for advanced RCC,” Professor Jun Guo, MD, PhD, from Peking University Cancer Hospital, stated in a press release.¹ “However, no such treaments have been approved in China. The approval of toripalimab’s new indications opens a new chapter in combined targeted therapy and immunotherapy in China, and it will transform current clinical practices for advanced RCC and introduce new treatment options for medium to high-risk patients!”

The multicenter, randomized, open-label, active-controlled phase 3 study enrolled patients with unresectable or metastatic clear cell RCC with or without sarcomatoid components who had not previously received systemic treatment and at least 1 measurable lesion by RECIST v1.1 criteria.² Patients were also required to have intermediate- or poor-risk disease per International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria and an ECOG performance status of 0 or 1.

Study participants were randomly assigned 1:1 to receive 240 mg of toripalimab every 3 weeks plus 5 mg of axitinib twice daily or 50 mg of sunitinib once daily for weeks of a 6-week cycle or 2 weeks of a 3-week cycle. They continued to receive treatment until intolerable toxicity or progressive disease. Patients were stratified by IMDC risk group (intermediate vs poor).

The primary end point was PFS by BICR and RECIST v1.1 criteria, and secondary end points included overall response rate (ORR), overall survival (OS), investigator-assessed PFS, duration of response (DOR), disease control rate (DCR), 1- and 2-year OS rates, and safety.

The median patient age was 60.0 years (range, 20-78), with 67.2% of patients under the age of 65 years. More than half of patients were male (75.8%), and 51.8% had an ECOG performance status of 0. Moreover, 56.8% of patients had a Karnofsky performance status score of 90 to 100, and 43.2% had a score ranging from 70 to 80. With regard to IMDC risk group, 81.5% had intermediate-risk disease and the remaining 18.5% had poor-risk disease. Sixty-one percent of patients had 2 or more organs with metastatic disease. The sites of metastases included the lung (68.6%), bone (21.6%), and liver (15.4%). More than half of patients (62.2%) had prior nephrectomy.

Additional data presented at the 2023 ESMO Congress indicated that the doublet outperformed sunitinib across all subgroups assessed on the study.

The investigator-assessed median PFS with toripalimab plus axitinib was 18.0 months (95% CI, 14.9-20.4) vs 10.4 months (95% CI, 8.4-12.4) with sunitinib alone (stratified HR, 0.57; 95% CI, 0.44-0.75; P < .0001). The 12-month PFS rates in these respective arms were 64.8% and 43.7%, and the 24-month PFS rates were 40.4% and 17.8%.

Moreover, the doublet elicited an ORR of 51.9% by BICR assessment vs 27.0% with sunitinib monotherapy (P < .0001). By investigator assessment, these respective rates were 56.2% and 29.9%. The median DOR by BICR with toripalimab plus axitinib was NE (95% CI, 20.5-NE) vs 16.7 months (95% CI, 9.7-NE) with sunitinib (stratified HR, 0.614; 95% CI, 0.340-1.137).

The OS with the doublet was NE (95% CI, NE-NE) vs 26.8 months (95% CI, 24.5-NE) with sunitinib alone (stratified HR, 0.61; 95% CI, 0.40-0.92; nominal P = .0186). The 12- and 24-month OS rates in the toripalimab/axitinib arm were 90.5% and 71.8%; in the sunitinib-alone arm, these respective rates were 81.9% and 63.2%.

In terms of safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.5% of those who received the doublet vs 99.5% of those given the monotherapy; 71.2% and 67.1% of these effects, respectively, were grade 3 or higher in severity. Serious AEs occurred in 44.7% of those who received toripalimab plus axitinib vs 28.6% of those given sunitinib. Immune-related toxicities occurred in 35.1% of those who received toripalimab plus axitinib vs 0.5% of those given sunitinib; these AEs were grade 3 or higher for 14.4% of those in the doublet arm. Infusion-related reactions were experienced by 4.3% of those in the toripalimab/axitinib arm.

TEAEs led to dose interruption of any of the agents for 69.2% of those in the doublet arm vs 43.3% of those in the monotherapy arm, and discontinuation rates were 14.4% and 8.1%, respectively. In the doublet arm, 3.8% of patients experienced TEAEs that resulted in death; this rate was 2.4% in the monotherapy arm.

The treatment-related AEs reported in 20% or more of patients in either group included hypertension, hypothyroidism, proteinuria, diarrhea, increased aspartate and alanine aminotransferase, fatigue, increased blood thyrotropin hormone, hand-foot syndrome, weight loss, anemia, decreased platelet count, increased blood creatinine, decreased white blood cell count, and decreased neutrophil count.

With this regulatory decision, toripalimab is the first immunotherapy approved for patients with renal cell carcinoma in China, according to a press release issued by Shanghai Junshi Biosciences Co., Ltd.1

References

1. Junshi Biosciences announces approval of the sNDA for toripalimab for the 1st-line treatment of renal cancer. News release. Shanghai Junshi Biosciences Co., Ltd. April 7, 2024. Accessed April 9, 2024. https://www.junshipharma.com/en/junshi-biosciences-announces-approval-of-the-snda-for-toripalimab-for-the-1st-line-treatment-of-renal-cancer/
2. Sheng X, Ye M, Zou Q, et al. 1882O RENOTORCH: Toripalimab combined with axitinib versus sunitinib in first-line treatment of advanced renal-cell carcinoma (RCC) – a randomized, open-label, phase III study. Ann Oncol. 2023;34(suppl 2):S1011-S1012. doi:10.1016/j.annonc.2023.09.1112