Neoadjuvant Anti-PD-1 Immunotherapy With Chemotherapy in Resectable Locally Advanced Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma.

Detailed Description
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On the basis of preliminary study, this study is to further verify the efficacy and safety of neoadjuvant anti-PD-1 immunotherapy plus chemotherapy. The further purpose of this study is to investigate the survival benefit of neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy compared with TP chemotherapy or up-front surgery in resectable locally advanced oral squamous cell carcinoma. And on this basis, the investigators will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.

Official Title
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A Multi-Center, Randomized Phase III Study of Neoadjuvant Anti-PD-1 Immunotherapy Plus TP Chemotherapy Versus TP Chemotherapy or Up-Front Surgery in Resectable Locally Advanced Oral Squamous Cell Carcinoma

Conditions
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Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab plus TP
* Drug: TP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented oral squamous cell carcinoma (biopsy required). Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-3M0, T3-4aN0-3M0) with resection option for potential cure, as assessed by a faculty surgeon at Hospital of Stomatology, Wuhan University. Distant metastasis is excluded by chest CT and emission computed tomograph. Adequate organ function as follows: 1) Leukocyte count ≥ 2,000/mm3; 2) Absolute neutrophil count ≥ 1,000/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum albumin ≥30 g/L; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN; 8) ALP ≤ 2.5 × ULN; 9) Prothrombin time-international normalized ratio ≤ 1.5; 10) Serum creatinine ≤ 1.5 × ULN; 11) INR/PT≤ 1.5; 12) TSH ≤ ULN. ECOG performance status 0-1. Female patient tested HCG negative in serum or urine within 7 days prior to the start of investigational product. Both patient and partner must agree to use contraception prior to study entry and for the duration of study participation and for up to 120 days after the last dose of PD-1 blockade. Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Exclusion Criteria: History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment. History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years. Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways. Active autoimmune disease or history of refractory autoimmune disease. Active systemic infection requiring therapy. Patients who are receiving psychotropic drug or alcohol/drug abuse. Subjects with concurrent other active malignancies. HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment. Uncontrollable systemic diseases, including diabetes, hypertension, etc. History of stroke or transient ischemic attack within past 6 months. Distant metastases or inability to resect after physician evaluation. Serious cardiovascular, respiratory, immune system critical disease or other conditions that the researchers thought might increase the subjects' risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Surgery followed by postoperative RT<br>The participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary. | |
| Experimental: Neoadjuvant TP chemotherapy<br>The participants will receive 2 courses of TP chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary. | Drug: TP<br>* The participants will receive docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.<br>* Other names: Docetaxel, Cisplatin;|
| Experimental: Neoadjuvant anti-PD-1 immunotherapy plus TP chemotherapy<br>The participants will receive 3 doses of PD-1 blockade and 2 courses of TP chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary. | Drug: Camrelizumab plus TP<br>* The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.<br>* Other names: SHR-1210 plus Docetaxel, Cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival (EFS) Rate on Each Treatment Arm. | EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1. | 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) on Each Treatment Arm. | OS is the time from randomization to death due to any cause. | 24 months. | 
| Radiographic Response. | Clinical response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy, as evaluated by radiographic examinations and defined by RECIST 1.1. Clinical response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy, as evaluated by radiographic examinations and defined by RECIST 1.1. | 8 weeks. | 
| Pathologic Response. | Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. Pathologic response is defined as sum of pathologic complete response and major pathologic response. Pathologic complete response is defined as the absence of viable residual tumor in resected specimen. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resected specimen. | 8 weeks. | 
| Adverse Events (AEs). | Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions. | 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant, Oral squamous cell carcinoma, Anti-PD-1 immunotherapy, Camrelizumab, TP chemotherapy