A Clinical Trial Comparing the Efficacy and Safety of Anyouping® and Platinum-based Chemotherapy With or Without Enlituo® in Advanced Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.

This study is a Phase II/III clinical trial, aimed to evaluate the efficacy and safety of Enlituo® combined with Anyouping® plus platinum and nab-paclitaxel chemotherapy as first-line therapy for advanced, recurrent or metastatic HNSCC.

Phase II Part Approximately 60 participants will be enrolled and randomly assigned at a 1:1 ratio to the experimental group.

Phase III Part Approximately 302 participants will be enrolled and randomly assigned in a 1:1 double-blind manner to the experimental group.

• Enlituo® + Anyouping® + PBC (Drug): Enlituo®：Enlituo® is administered according to the protocol. Anyouping®：Anyouping® is administered according to the protocol. Platinum-based chemotherapy (PBC)：Cisplatin (DDP) or Carboplatin (CBP) plus Albumin-bound Paclitaxel (nab-paclitaxel) are administered according to the protocol.
• Placebo-Enlituo + Anyouping® + PBC (Drug): Comparator in Phase 2 is Anyouping® + PBC. Comparator in Phase 3 is Placebo-Enlituo + Anyouping® + PBC. Placebo-Enlituo (only in Phase 3)：Placebo-Enlituo is administered according to the protocol. Anyouping®：Anyouping® is administered according to the protocol. Platinum-based chemotherapy (PBC)：Cisplatin (DDP) or Carboplatin (CBP) plus Albumin-bound Paclitaxel (nab-paclitaxel) are administered according to the protocol.

Primary outcomes

• Overall Survival (Phase 3) [Up to 2 years.]
• Objective Response Rate (Phase 2) [Up to 2 years.]

Secondary outcomes

• Duration of response [Up to 2 years.]: The Blinded Independent Imaging Review Committee (BIRC) and Investigators will evaluated，respectively in Phase 3.
• Disease control rate [Up to 2 years.]: The Blinded Independent Imaging Review Committee (BIRC) and Investigators will evaluated，respectively in Phase 3.
• Progression-Free Survival [Up to 2 years.]: The Blinded Independent Imaging Review Committee (BIRC) and Investigators will evaluated，respectively in Phase 3.
• Objective Response Rate (Phase 3) [Up to 2 years.]: The Blinded Independent Imaging Review Committee (BIRC) and Investigators will evaluated，respectively.
• Overall Survival (Phase 2) [Up to 2 years.]
• Time to Progression [Up to 2 years.]: The Blinded Independent Imaging Review Committee (BIRC) and Investigators will evaluated，respectively in Phase 3.
• Number of participants with treatment-related adverse events as assessed by CTCAE v6.0 [From the date of informed consent signature until 28 days after the last dose (each cycle is 21 days, up to 35 cycles or 2 years).]: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as assessed by CTCAE V6.0. Incidence of AE leading to dose interruption, dose delay and treatment discontinuation.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Voluntarily sign the written informed consent form and be willing to comply with all requirements specified in the study protocol;
* Aged ≥ 18 years;
* Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (including oral cavity, oropharynx, hypopharynx, larynx), deemed incurable after local therapy;
* Have not received any systemic therapy for recurrent or metastatic disease. Note: If disease progression occurs during neoadjuvant/adjuvant therapy, concurrent radiotherapy, or within 6 months after treatment discontinuation, the anti-tumor therapy administered during neoadjuvant/adjuvant therapy or concurrent radiotherapy (including platinum-based chemotherapy, anti-EGFR monoclonal antibodies, PD-1/PD-L1 inhibitors, etc.) will be regarded as first-line systemic therapy, and such subjects will be excluded.

(Remark: Subjects previously treated with PD-1/PD-L1 inhibitors may be enrolled provided a washout period of ≥ 12 months is met.)

* Have at least one measurable evaluable target lesion per RECIST v1.1, or a measurable lesion with definitive radiological progression following local therapy, and the lesion must be suitable for repeated precise measurement;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no disease deterioration within 2 weeks prior to enrollment;
* For participants with oropharyngeal carcinoma, human papillomavirus (HPV) status test results based on tumor tissue samples must be available prior to enrollment.

Exclusion Criteria:

* Primary tumor site (any histologic type) located in nasopharynx, nasal cavity, paranasal sinus, salivary gland, thyroid or parathyroid gland, skin, or unknown primary origin;
* Participants who have been diagnosed with a malignancy other than squamous cell carcinoma of the head and neck within 3 years prior to enrollment. Exceptions include cured basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, and/or carcinoma in situ of the cervix and/or breast cancer treated with curative resection;
* Participants with an expected survival of less than 6 months and/or rapidly progressive disease (e.g., participants experiencing rapid disease progression within 1-2 months during therapy planned prior to enrollment);
* Participants eligible for curative-intent local therapy;
* Pregnant or breastfeeding participants, or those planning pregnancy or conception during the anticipated study period (from screening visit through 180 days after the last dose);
* Known history of psychiatric disorder or substance abuse that would interfere with compliance with study requirements;
* Any other condition that renders the participant unsuitable for enrollment in the opinion of the investigator.