Junshi PD-1 Kidney Cancer Indication Approved to Fill the Gap of "Immune + Targeted" Treatment for Kidney Cancer in China

On April 7, 2024, Beijing time, Junshi Biosciences (1877. HK, 688180.SH) announced that the New Drug Application (NDA) for the first-line treatment of patients with intermediate-high-risk unresectable or metastatic renal cell carcinoma (CNC), an anti-PD-1 monoclonal antibody drug developed ® by the Company, in combination with axitinib for the first-line treatment of patients with intermediate- and high-risk unresectable or metastatic renal cell carcinoma, has recently been approved by the National Medical Products Administration (NMPA). This is the eighth indication approved for toripalimab in China and the first approved immunotherapy for kidney cancer in mainland China.

Renal cancer is the third most common malignant tumor of the urinary system in the world, and renal cell carcinoma (RCC) accounts for 80%~90% of all kidney cancer cases[1]. According to statistics, there were about 77,000 new cases and 46,000 deaths of kidney cancer in China in 2022 [2]. Approximately one-third of patients with renal cancer have distant metastases at the time of initial diagnosis, while 20-50% of patients with localized cancer who have undergone nephrectomy still have distant metastases [3][4]. Based on the risk classification of the International Alliance of Metastatic RCC Databases, the median overall survival (OS) of patients with low-, intermediate, and high-risk metastatic RCC who received anti-vascular targeted therapy was 35.3, 16.6, and 5.4 months, respectively[1][5]. Therefore, compared with low-risk patients, patients with intermediate- and high-risk advanced RCC have a more urgent clinical need for new treatment regimens.

THE APPROVAL OF THIS NEW INDICATION IS BASED ON DATA FROM THE RENOTORCH STUDY (NCT04394975). The RENOTORCH study is a multicenter, randomized, open-label, active-drug controlled phase III clinical study, conducted by Professor Guo Jun from Peking University Cancer Hospital and Professor Huang Yiran from Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in 47 clinical centers across the country, and is the first pivotal phase III clinical study of immunotherapy for advanced kidney cancer in mainland China.

A total of 421 patients with intermediate- and high-risk unresectable or metastatic RCC were randomized 1:1 to toripalimab plus axitinib (n=210) or sunitinib (n=211). The primary endpoint was progression-free survival (PFS) as assessed by an independent review committee (IRC), and the secondary endpoints included investigator-assessed PFS, IRC or investigator-assessed objective response rate (ORR), duration of response (DoR), disease control rate (DCR), overall survival (OS), and safety.

Previously, RENOTORCH's research results were presented for the first time at the 2023 European Society for Medical Oncology (ESMO) Congress, and the full text was simultaneously published in the Annals of Oncology (Impact Factor: 50.5; top 5 journals in the field of oncology). The study data showed that compared with sunitinib monotherapy, treatment with toripalimab plus axitinib significantly prolonged PFS (median PFS: 18.0 vs. 9.8 months, P=0.0028), prolonged PFS by nearly 2-fold, and reduced the risk of disease progression or death by 35% (hazard ratio [HR]=0.65; 95%CI: 0.49, 0.86). In addition, toripalimab had a better ORR (56.7% vs. 30.8%, P<0.0001), a longer DoR (median DoR: not reached vs. 16.7 months; HR=0.61), a clear trend towards OS benefit (median OS: not reached vs. 26.8 months), and a 39% lower risk of death (HR=0.61; 95% CI: 0.40, 0.92). In terms of safety, the safety and tolerability of toripalimab in combination with axitinib were good, and no new safety signals were found.

Professor Guo Jun from Peking University Cancer Hospital said: "At the global level, targeted combination immunotherapy has become the standard treatment for advanced kidney cancer, but there is no approval for this field in China. The approval of toripalimab for a new indication opens a new chapter in the target-immune combination of advanced kidney cancer in China, which will completely rewrite the clinical practice of advanced kidney cancer in mainland China, and more importantly, bring new treatment options to medium and high-risk patients."

Professor Huang Yiran from Renji Hospital, Shanghai Jiao Tong University School of Medicine, said: "The treatment of advanced kidney cancer is limited, especially the prognosis of intermediate- and high-risk patients is very unsatisfactory. The approval of toripalimab combined with axitinib therapy fills the gap in the first-line immunotherapy of kidney cancer in the Chinese population, and compared with targeted drug monotherapy, toripalimab target-immune combination therapy can significantly improve the PFS of patients, which will bring good news to the majority of advanced kidney cancer patients in mainland China. ”

Dr. Jianjun Zou, General Manager and CEO of Junshi Biosciences, said, "We would like to thank all the medical workers, patients and R&D personnel who participated in the RENOTORCH study for their dedication, so that China's kidney cancer immunotherapy can achieve 'zero breakthrough'!

[References]

[1]. National Health Commission of the People's Republic of China. Guidelines for the diagnosis and treatment of renal cell carcinoma (2022 edition). 2022.

[2]. Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl) 2022;135:584-90.

[3]. Padla Sa, Barsauk A, Thandra KC, et al. Epidemiology of renal cell carcinoma. World Oncol 2020;11:79-87.

[4]. Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 2003;30:843-52.

[5]. Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 2009; 27:5794-9.

About toripalimab injection (Tuoyi ®)

As the first domestic PD-1 monoclonal antibody drug approved for marketing in mainland China, toripalimab injection (Tuoyi ®) was supported by major national science and technology projects, and won the highest award in the field of national patents, "China Patent Gold Award".

To date, toripalimab has conducted more than 40 clinical studies in more than 15 indications around the world, including China, the United States, Southeast Asia and Europe. Ongoing or completed pivotal clinical studies evaluating the safety and efficacy of toripalimab in multiple tumor types, including lung, nasopharyngeal, esophageal, gastric, bladder, breast, liver, kidney and skin cancers.

To date, toripalimab has been approved for 8 indications in China: for the treatment of unresectable or metastatic melanoma that has failed prior systemic therapy (December 2018); Treatment of patients with metastatic nasopharyngeal carcinoma (February 2021), treatment of locally advanced or metastatic urothelial carcinoma that has failed platinum-based chemotherapy, including neoadjuvant or adjuvant chemotherapy progression within 12 months (April 2021), first-line treatment of patients with locally recurrent or metastatic nasopharyngeal carcinoma in combination with cisplatin and gemcitabine (November 2021), combination of paclitaxel and cisplatin for unresectable locally advanced/ First-line treatment for patients with recurrent or distant metastatic esophageal squamous cell carcinoma (May 2022) in combination with pemetrexed and platinum in epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK)-negative, First-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer (September 2022), perioperative treatment in combination with chemotherapy followed by this product as adjuvant therapy as an adjuvant therapy in adult patients with resectable stage IIIA-IIIB non-small cell lung cancer (December 2023), and first-line treatment in combination with axitinib in patients with intermediate- and high-risk unresectable or metastatic renal cell carcinoma (April 2024). In December 2020, toripalimab passed the national medical insurance negotiation for the first time, and 6 approved indications have been included in the National Medical Insurance Catalogue (2023), which is the only anti-PD-1 monoclonal antibody drug for the treatment of melanoma in the catalogue.

In terms of international layout, toripalimab has been approved in the United States as the first nasopharyngeal cancer drug, and it has been granted 2 Breakthrough Therapy Designations, 1 Fast Track Designation, 1 Priority Review Designation and 5 Orphan Drug Designations by the U.S. Food and Drug Administration (FDA) in the fields of mucosal melanoma, nasopharyngeal carcinoma, soft tissue sarcoma, esophageal cancer and small cell lung cancer.

In December 2022 and February 2023, the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Agency (MHRA) accepted marketing authorization applications (MAAs) for toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic nasopharyngeal carcinoma, and in combination with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic esophageal squamous cell carcinoma, respectively. In November 2023 and January 2024, the Therapeutic Goods Administration (TGA) of Australia and the Health Sciences Authority (HSA) of Singapore accepted toripalimab in combination with cisplatin/gemcitabine as first-line treatment for adult patients with metastatic or recurrent locally advanced nasopharyngeal carcinoma, and as monotherapy for recurrent, Marketing authorization application for adult patients with unresectable or metastatic nasopharyngeal carcinoma, of which the TGA granted 1 orphan drug designation and the HSA granted 1 priority review designation.

About Junshi Biosciences

Junshi Biosciences (688180.HK) SH, 1877.HK) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapies. Relying on the global integrated source innovation and R&D capabilities, the company has built a multi-level product pipeline covering more than 50 innovative drugs, covering five major therapeutic areas of malignant tumors, autoimmunity, chronic metabolism, nervous system and infectious diseases, and has 4 products marketed in China or overseas, including the first PD-1 inhibitor toripalimab (Tuoyi ®), which was independently developed in mainland China and approved for marketing in China and the United States, with more than 30 drugs in the clinical development stage. During the epidemic, Junshi Biosciences also participated in the development of a number of innovative drugs for the prevention and treatment of new crowns, such as etesevimab and Medwei ®, and actively assumed the responsibility of local innovative pharmaceutical companies.

With the mission of "building a world-class and trustworthy bio-derived drug for all-inclusive patients", Junshi Biosciences is based in China and has a global layout. At present, the company has about 3,000 employees worldwide, located in San Francisco and Maryland in the United States, Shanghai, Suzhou, Beijing and Guangzhou in China.