Efficacy and Safety of Neoadjuvant Pembrolizumab in III-IVA Resectable Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this prospective, single-center, single-arm, open-label II phase observation clinical trial is to evaluate the efficacy and safety of Pembrolizumab immunoadjuvant therapy in patients with stage III-IVA oral squamous cell carcinoma. The primary end point is the pathological tumor remission rate of the primary tumor and regional lymph nodes after neoadjuvant immunotherapy (pTR-2: the proportion of necrotic tumor cells, keratin fragments and giant cells in tissue sections > 50%). The secondary endpoints are 1-year disease-free survival (DFS), 1-year overall survival (OS) and the incidence of adverse events, compared with historical data. In addition, we will check the relevant immune indicators, such as PD-L1 and CPS scores.

Official Title
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Efficacy and Safety of Neoadjuvant Pembrolizumab in III-IVA Resectable Oral Squamous Cell Carcinoma

Conditions
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Oral Cavity Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 Male and female Patients histologically or cytologically difined as oral cavity squamous cell carcinoma According to the American Joint Committee on Cancer ( AJCC 8th Edition ) , patients with resectable stage III-IVA OCSCC ECOG performance status ≤ 1 Patients with normal bone marrow and organ function as defined below: Blood routine examination: Absolute neutrophil count ≥ 1.5×109/L; Platelets ≥ 100.0×109/L; Hemoglobin ≥ 9.0 g/dL. Liver function: Totle bilirubin ≤ 2.0×ULN(Upper Limit Of Normal); Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase 2.5×ULN; Albumin ≥ 2.8g/dL. Renal function: (1)Creatinine clearance rate > 60.0ml/min. Coagulation function: (1)International Normalized Ratio ≤ 1.5；Activated Partial Thromboplastin Time ≤ 1.5×ULN Prior to and during study, and lasting 120 days for the final utilization of pembrolizumab, patients approve of contraception Patients voluntarily agree to participate in the study and sign the informed consent form Exclusion Criteria: Prior treatment for OCSCC (sugery, immunotherapy, radiotherapy, chemotherapy) Patients with metastatic OCSCC with an unknown primary tumor site Patients with infectious disease: AIDS, hepatitis, active tuberculosis Received a live vaccine within 30 days prior to the first dose of pembrolizumab. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guérin ( BCG ), typhoid vaccine, or attenuated flu vaccine 5.Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab Currently receiving any other investigational agents Has a history of allergic reactions attributed to compounds of similar chemical of biologic composition to pembrolizumab or other agents used in the study Patients with ongoing or active infectoin requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, underlying pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements Has a or more active autoimmune disease Has a history( non-infectious ) pneumonitis that required steroids or current pneumonitis

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pembro Neoadjuvant + SOC Adjuvant<br> | Drug: Pembrolizumab<br>* Participants receive 200 mg pembrolizumab as a neoadjuvant by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles before surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pathologic tumor response-2（pTR-2） | The proportion of participants with a pathologic tumor response-2（pTR-2）as assessed by the Central Pathologist at the time of definitive surgery. pTR-2 is defined as the proportion of necrotic tumor cells, keratin fragments and giant cells in tissue sections > 50% | Up to 30 days post-sugery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS) | DFS is the time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence as assessed with imaging or biopsy as indicated; or death due to any cause | Up to 1 year | 
| Overall Survival (OS) | OS is the time from surgery to death due to any cause. | Up to 1 year | 
| Adverse Events (AEs) | Participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy | From time of first dose of study treatment until the end of follow-up (up to 1 year) |