Clinical trial NCT06107114: Cetuximab+Zimberelimab in Combination With Cisplatin and Nab-paclitaxel in Resctable Head and Neck Squamous Cell Carcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hend and Neck Squamous Cell Carcinoma Locally Advanced Operable
Keywords: head and neck squamous cell carcinoma
Cetuximab
Zimberelimab
neoadjuvant therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-10-30
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: ORR
timeFrame: 9 weeks
Secondary outcomes:
measure: PCR
timeFrame: 9 weeks
measure: MPR
timeFrame: 9 weeks
measure: DCR
timeFrame: 2 years
measure: PFS
timeFrame: 2 years
measure: OS
timeFrame: 5 years
measure: Adverse Events Graded By Ctcae V5.0
timeFrame: 90 days after the first dose of study treatment
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat Sun University Cancer Center, 651 Dongfeng East Road
name: Xuekui Liu
role: PRINCIPAL_INVESTIGATOR
References: