Neoadjuvant treatment for operable head and neck cancer

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 testing a new combination treatment for patients with operable head and neck cancer to see if it helps shrink tumors before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: Cadonilimab, chemotherapy
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT06023875 on ClinicalTrials.gov

What this trial studies

This phase 2 trial investigates the use of Cadonilimab in combination with cisplatin and Nab-paclitaxel as a neoadjuvant therapy for patients with resectable head and neck squamous cell carcinoma (HNSCC). The study will enroll 30 patients with specific clinical stages of HNSCC who are eligible for surgery. The primary outcome measure will be the objective response rate to the treatment prior to surgical intervention. The trial aims to evaluate both the efficacy and safety of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with newly diagnosed, operable head and neck squamous cell carcinoma at specific clinical stages.

Not a fit: Patients with distant metastases or those with significant comorbidities affecting organ function may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve surgical outcomes and overall survival for patients with head and neck cancer.

How similar studies have performed: Other studies have shown promising results with similar neoadjuvant therapies in head and neck cancers, indicating potential for success.

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 (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.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Sun Yat-sen University Cancer Center, 651 Dongfeng East Road — Guangzhou, Guangdong, China (Recruiting)
• Sun Yat-sen University Cancer Center, 651 Dongfeng East Road — Guangzhou, China (Recruiting)

Study contacts

• Study coordinator: Xuekui Liu

Conditions Head and Neck Squamous Cell Carcinoma; Locally Advanced Operable; head and neck squamous cell carcinoma; Cadonilimab; neoadjuvant therapy