Neoadjuvant Cadonilimab in Combination With Cisplatin and Nab-paclitaxel in Resectable Head and Neck Squamous Cell Carcinoma (NCCCNRHNSCC)

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

This study is a single arm phase ll trial including 30 patients with T2N2-3M0、T3-4N0-3M0 (lll-V) head and neck squamous cell carcinoma (HNSCC) eligible forresection, who receive neo-adjvuant Cadonilimab combined with cisplatin and Nab.paclitaxel.This proposed study will evaluate the efficacy and safety of preoperativeadministration of Cadonilimab combined with chemotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC) who are about to undergo surgery.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma; Locally Advanced Operable
• Intervention / Treatment: Drug: Cadonilimab; Drug: Docetaxel; Drug: Cisplatin

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): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuekui Liu; Phone Number: +8613609713406; Email: liuxk@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center, 651 Dongfeng East Road
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center, 651 Dongfeng East Road
      • Contact: Xiaoyun Feng; Phone Number: +8615900033919; Email: 1056608539@qq.com

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 (III-IV) (AJCC 8th edition staging).
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 ≥ 4000/μL, neutrophils ≥ 2,000/μL, 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;
   3. Renal function: Serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 60 mL/min according to Cockcroft-Gault formula.
9. Consent to provide archived tumor tissue samples or undergo biopsy for collection of tumor lesion tissue (at least 3 unstained FFPE pathological slides, if deemed insufficient for PD-L1 IHC testing by the central laboratory, an additional 3 unstained FFPE pathological slides should be provided) to be sent to the central laboratory for PD-L1 immunohistochemistry (IHC) testing (preferably using recently obtained tumor tissue samples). Tumor lesions planned for biopsy should not be used for assessing target lesions of the disease unless no other suitable lesions for biopsy are available. 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. Active or prior history of documented inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
12. Women of childbearing potential with a positive pregnancy test and breastfeeding women.
13. Known active pulmonary tuberculosis (TB). Subjects suspected of having active TB need clinical evaluation for exclusion.
14. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
15. Severe infection occurring within 4 weeks before the first administration, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
16. Subjects planning major surgery within 30 days after the first dose of AK104 in combination with platinum-containing dual-agent therapy (as determined by the investigator), or not yet fully recovered from prior surgery. Local surgical procedures (such as placement of a systemic port and prostate biopsy) are allowed provided that the surgery is completed at least 24 hours before the first dose of the study treatment.

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: Cadonilimab; Cadonilimab 10mg/kg. The drug was administered every 3 weeks (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.; Other Names: AK104; 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.

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
PFS	progression-free survival	2 years
PCR	Pathological Complete Response	9 weeks
Adverse Events Graded By Ctcae V5.0	Percentage of adverse events that are possibly, probably or definitely 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

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: September 4, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; head and neck squamous cell carcinoma; Cadonilimab
• 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; Docetaxel
• Other Study ID Numbers: 2023-FXY-011-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