Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma

NCT04649476 | Completed Phase 2 Results

• 1 other identifier: HStomatologyWuhan
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oral Squamous Cell Carcinoma

Keywords

Neoadjuvant; Oral squamous cell carcinoma; PD-1 blockade; Camrelizumab; TPF induction chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Radiographic Response.

  8 weeks.

• Event-free Survival (EFS) Rate on Each Treatment Arm.

  24 months.

• Overall Survival (OS) on Each Treatment Arm.

  24 months.

• Adverse Events (AEs).

  24 months.

Other Outcomes (1)

• Changes in the Level of Circualting Exosomal PD-L1.

  24 months.

Study Arms (2)

Neoadjuvant PD-1 blockade alone

EXPERIMENTAL

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

Neoadjuvant PD-1 blockade plus TPF induction chemotherapy

EXPERIMENTAL

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

Interventions

Camrelizumab DRUG

The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.

Also known as: SHR-1210

Neoadjuvant PD-1 blockade alone

Camrelizumanb plus TPF DRUG

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.

Also known as: Docetaxel, Cisplatin, 5-Fluorouracil

Neoadjuvant PD-1 blockade plus TPF induction chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital of Stomatology, Wuhan University: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Hospital of Stomatology, Wuhan University

Wuhan, Hubei, 430079, China

Location

Related Publications (2)

• Liu YT, Liu HM, Ren JG, Zhang W, Wang XX, Yu ZL, Fu QY, Xiong XP, Jia J, Liu B, Chen G. Immune-featured stromal niches associate with response to neoadjuvant immunotherapy in oral squamous cell carcinoma. Cell Rep Med. 2025 Mar 18;6(3):102024. doi: 10.1016/j.xcrm.2025.102024.

  PMID: 40107247 DERIVED

• Liu HM, Xiong XP, Yu ZL, Shao Z, Chen GL, Liu YT, Wang XX, Fu QY, Cheng XX, Li J, Zhang JL, Li B, Gong HY, Zhong YH, Zhang W, Jia J, Liu B, Chen G. Neoadjuvant immunotherapy with or without chemotherapy in locally advanced oral squamous cell carcinoma: Randomized, two-arm, phase 2 trial. Cell Rep Med. 2025 Feb 18;6(2):101930. doi: 10.1016/j.xcrm.2025.101930. Epub 2025 Jan 30.

  PMID: 39889711 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

camrelizumab; Docetaxel; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gang Chen, MD
• Organization: Hospital of Stomatology, Wuhan university

geraldchan@whu.edu.cn

+86 02787686215

Study Officials

• Gang Chen, MD

  Hospital of Stomatology, Wuhan University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, Professor

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: December 2, 2020
• Study Start: March 22, 2021
• Primary Completion: August 10, 2022
• Study Completion: August 10, 2024
• Last Updated: January 10, 2025
• Results First Posted: April 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)