Objective Response Rate of Ivonescimab With Chemotherapy in Locally Advanced Resectable Oral and Oropharyngeal Squamous Cell Carcinoma

Two cycles of treatment with Ivonescimab combined with chemotherapy were administered, with an interval of 3 weeks between the two cycles. Oral swab and saliva samples were collected within 3 days prior to the initiation of the first cycle of Ivonescimab plus chemotherapy, within 3 days prior to the initiation of the second cycle, and within 3 days prior to surgery. Intraoperatively, tumor tissues and paracancerous tissues were harvested. A 3 mm-thick section of the resected primary tumor lesion was obtained for pathological examination to investigate the tumor regression pattern.

• Ivonescimab（AK112，a PD-1/VEGF bispecific antibody） (Drug): Patients received two cycles of Ivonescimab combined with chemotherapy at a 3-week interval. The therapeutic regimen consisted of Ivonescimab (10 mg/kg) in combination with paclitaxel (135-175 mg/m²) plus cisplatin (80-120 mg/m²) or carboplatin (0.3-0.4 g/m²). Oral swabs and saliva samples were collected within 3 days prior to the initiation of the first cycle of Ivonescimab plus chemotherapy, within 3 days prior to the initiation of the second cycle, and within 3 days prior to surgery. Intraoperatively, tumor tissues and paracancerous tissues were harvested, and a 3 mm-thick section of the resected primary tumor lesion was obtained for pathological examination to investigate the tumor regression pattern.

Primary outcomes

• ORR [Up to 8 weeks]: According to RECIST version 1.1, it is defined as the proportion of patients who achieved Complete Response (CR) or Partial Response (PR).

Secondary outcomes

• Tumor regression Pattern [Perioperative/ Periprocedural]: Classification of tumor regression as concentric or non-concentric based on pathological assessment of resected primary tumor specimens. Concentric regression pattern: The residual tumor presents as a single mass with scattered microscopic satellite foci in the surrounding tissues. Non-concentric regression pattern: The tumor dissociates into multiple discretenlesions and is widely scatterd within the stroma.
• Two-year progression-free survival rate [2 Years]: The proportion of patients who remain alive and progression-free for 2 years after treatment

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Histopathologically diagnosed as oral squamous cell carcinoma (OSCC) or oropharyngeal squamous cell carcinoma (OPSCC)
2. Patients staged according to the AJCC criteria (8th edition) as locally advanced (Stage III/IVA oral cancer, HPV-negative oropharyngeal cancer, or Stage II/III HPV-positive oropharyngeal cancer) and assessed by the investigators as resectable.
3. Age 18 to 80 years
4. Complete blood count (CBC): White blood cell (WBC) count ≥3×10⁹/L; Platelet (PLT) count ≥75×10⁹/L; Hemoglobin (Hb) concentration ≥80g/L
5. Liver function: Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN)
6. Kidney function: Estimated glomerular filtration rate (eGFR) > 50 mL/min
7. Patients must have adequate function of vital organs (including cardiac, pulmonary, thyroid, and other organs) and a general condition that allows tolerance of the treatment regimen of this study.
8. Sign the Informed Consent Form (ICF)

Exclusion Criteria:

1. Pregnancy or lactation (for female participants)
2. A history of epilepsy or mental illness that is not effectively controlled
3. Unresolved toxicities of grade > 2 per CTCAE criteria resulting from prior anticancer therapy
4. Other conditions deemed unsuitable for study participation by the investigators, including patients with autoimmune diseases or those at high risk of bleeding due to various causes