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 internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells.

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^®). Currently, there are six approved indications for toripalimab in China:

• 1. unresectable or metastatic melanoma after failure of standard systemic therapy;
• 2. in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic nasopharyngeal carcinoma (“NPC”)；
• 3. recurrent or metastatic NPC after failure of at least two lines of prior systemic therapy;
• 4. locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
• 5. in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (“ESCC”);
• 6. in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small-cell lung cancer (“NSCLC”).

The first three indications have been included in the National Reimbursement Drug List (“NRDL”) (2022 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for melanoma.

In the United States, the FDA is reviewing the Biologics License Application (“BLA”) resubmission for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic nasopharyngeal carcinoma (“NPC”) and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy. 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”).

In Europe, the European Medicines Agency (EMA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) accepted the marketing authorization application (MAA) in December 2022 and February 2023 for: 1) toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab in combination with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC.

Mechanism of Action

PD-1 is a T cell surface receptor; it is an immune checkpoint molecule in the co-inhibitory signal pathway of the T cell. As shown in the following figure, the binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to the inhibition of T-cell activation and immune surveillance of tumor cells. Anti-PD-1 monoclonal antibodies can block the PD-1/PD-L1 pathway and thereby restore the immune function of T cells.

Main research literature

• Serial number Journal name Document title Published on Link
• 1 Cancer Cell Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial 2022
• 2 Journal of Clinical Oncology Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01) 2022
• 3 Journal for ImmunoTherapy of Cancer Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis 2022
• 4 Clinical Cancer Research Safety, Efficacy, and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03 2022
• 5 Annals of Oncology Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial 2022
• 6 Nature Medicine Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial 2021
• 7 Signal Transduction and Targeted Therapy Toripalimab plus chemotherapy as second-line treatment in previously EGFRTKIs treated patients with EGFR-mutant advanced NSCLC: a multi-center phase II trial 2021
• 8 Journal of Clinical Oncology Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02) 2021
• 9 JAMA Network Open Safety, Antitumor Activity, and Pharmacokinetics of Toripalimab, a Programmed Cell Death 1 Inhibitor, in Patients With Advanced Non–Small Cell Lung Cancer A Phase 1 Trial 2020
• 10 Cancer Communications A Phase I Study of Toripalimab, an anti-PD-1 Antibody, in Patients With Refractory Malignant Solid Tumors 2020
• 11 Clinical Cancer Research Safety, Efficacy and Biomarker Analysis of Toripalimab in previously treated advanced melanoma: results of the POLARIS-01 multicenter phase II trial 2020
• 12 European Journal of Cancer Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study 2020
• 13 mABs Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy 2019
• 14 Acta Pharmacologica Sinica Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001 2017
• 15 Clinical Cancer Research Efficacy, safety and biomarkers of toripalimab in patients with recurrent or metastatic neuroendocrine neoplasms：a multiple-center phase Ib trial 2020
• 16 Journal of Clinical Oncology Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial 2019
• 17 Annals of Translational Medicine JS001, an anti-PD-1 mAb for advanced triple negative breast cancer patients after multi-line systemic therapy in a phase I trial 2019
• 18 Annals of Oncology Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemorefractory gastric cancer treated with toripalimab, a PD1 antibody in phase Ib/II clinical trial NCT02915432 2019
• 19 Journal of Hematology & Oncology Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients 2019