Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma (NEOPBOSCC)

A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.

Study Overview

• Status: Completed
• Conditions: Oral Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Camrelizumab; Drug: Camrelizumanb plus TPF

Detailed Description

The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we 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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hospital of Stomatology, Wuhan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically documented oral squamous cell carcinoma (biopsy required).
2. 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.
3. Distant metastasis is excluded by chest CT and emission computed tomograph.
4. 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.
5. ECOG performance status 0-1.
6. 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.
7. Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form.

Exclusion Criteria:

1. History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment.
2. History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years.
3. 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.
4. Active autoimmune disease or history of refractory autoimmune disease.
5. Active systemic infection requiring therapy.
6. Patients who are receiving psychotropic drug or alcohol/drug abuse.
7. Subjects with concurrent other active malignancies.
8. HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment.
9. Uncontrollable systemic diseases, including diabetes, hypertension, etc.
10. History of stroke or transient ischemic attack within past 6 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant PD-1 blockade alone; The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.	Drug: Camrelizumab; The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.; Other Names: SHR-1210
Experimental: Neoadjuvant PD-1 blockade plus TPF induction chemotherapy; The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary.	Drug: Camrelizumanb plus TPF; 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, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.; Other Names: Docetaxel, Cisplatin, 5-Fluorouracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. Hematoxylin and eosin (H&E)-stained slides of entire tumor and all sampled lymph nodes were scanned and assessed by two independent pathologists. The entire tumor bed and all sampled lymph nodes were examined histologically in patients who had pathological complete response (pCR), which was defined as the absence of viable tumor in all slides. MPR was defined as the presence of 10% or less viable residual tumor in the resected tumor specimens. Pathological partial response (pPR) was defined as presence of more than 10% and less than 50% viable residual tumor and pathological non-response (pNR) was defined as presence of more than 50% viable residual tumor in the resected tumor specimens. Pathologic response was defined as sum of pCR and MPR.	8 weeks.

Secondary 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.
Overall Survival (OS) on Each Treatment Arm.	OS is the time from randomization to death due to any cause.	24 months.
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.
Radiographic Response.	Radiographic response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy were evaluated by enhanced computed tomography examinations and defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete Response (CR) was defined as disappearance of all target lesions. Partial Response (PR) was defined as >=30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) was defined as <20% increase and <30% decrease in the sum of the longest diameter of target lesions. Progressive disease (PD) was defined as >=20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.	8 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Level of Circualting Exosomal PD-L1.	The level of circulating exosomal PD-L1 at serial time points pre- and on-treatment, as detected by enzyme-linked immunosorbent assay (ELISA).	24 months.

Collaborators and Investigators

• Sponsor: Hospital of Stomatology, Wuhan University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Gang Chen, MD, Hospital of Stomatology, Wuhan University

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): August 10, 2024

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant; PD-1 blockade; Camrelizumab; Oral squamous cell carcinoma; TPF induction chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Fluorouracil; Cisplatin
• Other Study ID Numbers: HStomatologyWuhan

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No