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

Nanfang Hospital, Southern Medical University47 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Oral Cavity Squamous Cell Carcinoma

Interventions

PembrolizumabDRUG

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.

Medical Language ↔ Plain English

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: 1. Absolute neutrophil count ≥ 1.5×109/L; 2. Platelets ≥ 100.0×109/L; 3. Hemoglobin ≥ 9.0 g/dL. Liver function: 1. Totle bilirubin ≤ 2.0×ULN(Upper Limit Of Normal); 2. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase * 2.5×ULN; 3. 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

Outcomes

Primary Outcomes

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%

Time frame: Up to 30 days post-sugery

Secondary Outcomes

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

Time frame: Up to 1 year

Overall Survival (OS)

OS is the time from surgery to death due to any cause.

Time frame: 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

Time frame: From time of first dose of study treatment until the end of follow-up (up to 1 year)