Cetuximab+Zimberelimab in Combination With Cisplatin and Nab-paclitaxel in Resctable Head and Neck Squamous Cell Carcinoma (CZCNRHNSCC)

An Open, Single-center, Phase II Trial of Cetuximab+Zimberelimab Combined With Platinum-containing Dual-agent Neoadjuvant Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

This study is a single arm phase ll trial including 52 patients with T2N2-3M0#T3-4N0-3M0 (III-V) head and neck squamous cell carcinoma(HNSCC) eligible forresection, who receive Cetuximab+ Zimberelimab combined with cisplatin and Nab.paclitaxel.This proposed study will evaluate the efficacy and safety of preoperative administration of Cetuximab+ Zimberelimab combined with chemotherapy in Head and Neck Squamous Cell Carcinoma(HNSCC) who are about to undergo surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Hend and Neck Squamous Cell Carcinoma Locally Advanced Operable
• Intervention / Treatment: Drug: Docetaxel; Drug: Cisplatin; Drug: Cetuximab; Drug: Zimberelimab

Detailed Description

In this study, eligible subject will be enrolled into study arm to accept study treatment objective response rate will be the primary outcome measures.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuekui Liu; Phone Number: 08613609713406; Email: Liuxk@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed primary head and neck squamous cell carcinoma confirmed by histology and/or cytology (excluding diagnostic therapy).
2. Clinical stage:T2N2-3M0,T3-4N0-3M0 (AJCC 8th editionstaging).
3. Age: 18 to 70 years.
4. PS score (see Appendix Table 1; performance status score of 0 or 1).
5. Patients evaluated by a head and neck oncologist as resectable with no distant metastases.
6. Patients with at least one measurable lesion according to RECIST version 1.1 criteria.
7. Patients' toxicities assessed according to CTCAE version 4.03 criteria.

8. Patients with normal organ function (heart,brain, lungs, kidneys) and suitable for surgery:

   1. Hematology: White blood cells ≥ 3500/μL,neutrophils ≥1,800/pL, hemoglobin ≥ 9 g/dL, platelets ≥100,000/μL;
   2. Liver function: Bilirubin ≤ 1.5 times the upper limit of normal (ULN) (patients with known Gilbert's disease and serum bilirubin levels ≤ 3 times ULN can be included), AST and ALT ≤3 times ULN, alkaline phosphatase ≤ 3 times ULN; albumin ≥ 3 g/dL; c.Renal function: Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min according to Cockcroft-Gault formula.
9. Patients have signed an informed consent form, are willing and able to comply with the study's visit, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. History of severe hypersensitivity reactions to components of other monoclonal antibodies, CTLA4, or PD-1 antibodies.
2. Patients with known or suspected autoimmune diseases, including dementia and epileptic seizures.
3. Recurrence, distant metastasis, or the inability to undergo surgery as assessed by a head and neck physician.
4. Abnormal coagulation function:(PT > 16s,APTT>53s,TT> 21s, Fib < 1.5g/L), bleeding tendency, or currently on anticoagulant or thrombolytic therapy.
5. Severe heart disease, pulmonary dysfunction, patients with heart or lung function below Grade 3 (including Grade 3).
6. Laboratory values not meeting relevant criteria within 7 days prior to enrollment.
7. Previous use of anti-PD-1 antibodies, anti-PD-L1 antibodies,anti-PD-L2 antibodies, or anti-CTLA-4 antibodies (or any other antibodies targeting T cell co-stimulation or checkpoint pathways).
8. Pre-existing conditions requiring long-term use of immunosuppressive drugs or a need for systemic or local use of corticosteroids at immunosuppressive doses prior to enrollment.
9. HIV-positive individuals;HBsAg-positive individuals with positive HBV DNA copy number (quantitative test≥1000 cps/ml); positive chronic hepatitis C blood screening(HCV antibody positive).
10. Traditional herbal medicine used for anti-tumor purposes within 4 weeks before randomization.
11. Women of childbearing potential with a positive pregnancy test and breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental group; Patients with locally advanced operable head and neck squamous cell carcinoma

Drug: Docetaxel; Docetaxel 75mg/m2. Intravenous infusion was given every 3 weeks (Q3W), and 21 days (Q3W) was a treatment cycle. Treatment regimen is recommended for 3 cycles.; Drug: Cisplatin; Cisplatin 60mg/m2. Intravenous infusion was given every 3 weeks (Q3W), and 21 days (Q3W) was a treatment cycle. Treatment regimen is recommended for 3 cycles.; Drug: Cetuximab; Cetuximab 400mg/m2 (The first week), 250mg/m2(Follow-up weekly) The drug was administered every week (QW). The treatment regimen is recommended for three cycles until the researchers determine that the subjects cannot continue to benefit, until the disease progression (PD), the toxicity cannot be tolerated, the treatment is delayed by more than 14 days, or the patient withdraws the informed consent form or dies.; Drug: Zimberelimab; Zimberelimab 240 mg, The drug was administered every week (Q3W), and 21 days (Q3W) was a treatment cycle. The treatment regimen is recommended for three cycles until the researchers determine that the subjects cannot continue to benefit, until the disease progression (PD), the toxicity cannot be tolerated, the treatment is delayed by more than 14 days, or the patient withdraws the informed consent form or dies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	overall response rate	9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR	Major Pathological Response	9 weeks
OS	Overall survival	5 years
DCR	Disease Control Rate	2 years
PCR	pathological Complete Response	9 weeks
PFS	Progression-Free survival	2 years
Adverse Events Graded By Ctcae V5.0	Percentage of adverse events that are possibly, probably related to study treatment per Criteria for Adverse Events version 5(CTCAE v5.0)	90 days after the first dose of study treatment

Collaborators and Investigators

• Sponsor: Xuekui Liu
• Investigators: Principal Investigator: Xuekui Liu, Sun Yat Sun University Cancer Center, 651 Dongfeng East Road

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 24, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Cetuximab; neoadjuvant therapy; head and neck squamous cell carcinoma; Zimberelimab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cetuximab
• Other Study ID Numbers: 2023-FXY-099-HNC

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