Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients

Neoadjuvant Toripalimab and Paclitaxel/Cisplatin on Pathological Response in Oral Squamous Cell Carcinoma Patients: A Single-arm Phase I Trial

The aim of this study is to use the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathological response and safety will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will be the second endpoints.

In patients with locally advanced oral squamous cell carcinoma (OSCC), comprehensive treatment is recommended, including surgery, radiotherapy, chemotherapy and others. Pre-operative neoadjuvant therapy can reduce tumor burden, increase organ preservation rate, and reduce distant metastasis rate. Pre-operative neoadjuvant therapy with paclitaxcel and cisplatin (TP) has been used as one of recommended protocols in patients with locally advanced head and neck squamous cell caricnoma, including OSCC. Anti-PD1/PD-L1 immunotherapies have achieved exciting clinical outcomes in several malignancies, such as lung cancer, breast cancer, and so on. Recently, pre-operative neoadjuvant therapy with combination of immunotherapy and chemotherapy agents has been used with good pathological response, which might transfer to good clinical prognosis in patients with malignancies. However, pre-operative neoadjuvant therapy with combination of anti-PD1 and TP in OSCC patients has not been reported. The innovation of this study is the combination of immune checkpoint inhibitor of Toripalimab, and chemotherapy agents of TP, as a neoadjuvant therapy to treat the patients with locally advanced OSCC, followed with radical surgery and post-operative radiotherapy/chemoradiotherapy, the major pathological response and safety will be evaluated as the primary surrogate endpoints, the 2-year survival rate and local recurrence rate will be the second endpoints.

Inclusion Criteria:

• Eastern cooperative oncology group performance status (ECOG PS) score: 0-1 points
• Pathological diagnosis of oral squamous cell carcinoma (including tongue, gums, cheeks, mouth floor, hard palate, posterior molar region)
• Clinical stage of III/IVA (AJCC 2018)
• Blood routine: white blood cells > 3,000/mm3, hemoglobin > 8g/L, platelets > 80,000/mm3
• Liver function: Alanine Transaminase/Aspartate Transaminase <2.5 times the upper limit of normal, bilirubin <1.5 times the upper limit of normal
• Renal function: serum creatinine <1.5 times the upper limit of normal
• Sign the informed consent

Exclusion Criteria:

• There are still unresolved toxic reactions above CTCAE level 2 caused by previous anti-cancer treatment
• Grade 3-4 allergic reactions to Toripalimab, paclitaxcel or cisplatin
• Active severe clinical infection (> CTCAE 5.0 version 2 infection)
• Difficult to control hypertension or cardiovascular disease with clinical significance (such as activity)-such as cerebrovascular accident (< 6 months before treatment), myocardial infarction (< 6 months before treatment), unstable angina, New York Cardiology Society (NYHA Appendix 5) congestive heart failure grade II or above, or severe arrhythmia that cannot be controlled with drugs or has potential impact on experimental treatment
• Chronic diseases requiring immunotherapy or hormone therapy
• Women during pregnancy or lactation
• Participated in other clinical studies within 30 days before enrollment
• Other circumstances that the investigator thinks are not suitable for participating in the study