Monoclonal antibodies that target PD-1 or PD-L1 have been known to boost the body’s immune response against cancer cells. Anti-PD-1 antibodies have demonstrated effective treatment of several types of cancer, including melanoma of the skin, non-small cell lung cancer, kidney cancer, head and neck cancers, and Hodgkin’s lymphoma. Junshi Biosciences’ toripalimab is approved in China for the second-line treatment of melanoma, urothelial cancer, and nasopharyngeal carcinoma.
Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor endocytosis function. PD-L1 and PD-L2 are tumor checkpoint proteins which recognize the PD-1 receptor on T cells and exhaust their anti-tumor activity. Blocking PD-1 interactions with PD-L1 and PD-L2 is thought to recharge the immune system’s ability to attack and kill tumor cells.
Toripalimab also is thought to encourage efficient internalization (endocytosis) of the PD-1 receptor, enabling a Trojan Horse effect allowing T cells to slip undetected past the tumor PD-L1 and PD-L2 checkpoints.
In the United States, the FDA is reviewing the BLA resubmission for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic NPC and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy.
The toripalimab BLA is supported by the results from clinical studies “POLARIS-02” and “JUPITER-02”. The POLARIS-02 study is a multi-center, open-label, pivotal Phase II clinical study, the results of which were published online in January 2021 in the Journal of Clinical Oncology. The JUPITER-02 study is a randomized, double-blind, placebo-controlled, international multi-center Phase 3 clinical trial, the results of which were presented at the 2021 American Society of Clinical Oncology annual meeting in a Plenary Session presentation (#LBA2) and were published as the cover article of the September 2021 issue of Nature Medicine.
The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer ("SCLC").
More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.
In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI®). Toripalimab is approved in China for the second-line treatment of melanoma, nasopharyngeal carcinoma, urothelial cancer, esophageal cancer, and non-small cell lung cancer.
