A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Inclusion Criteria:

1. Be able and willing to provide written informed consent.

2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

3. Have a life expectancy of at least 3 months.

4. Has histologically confirmed diagnosis of R/M HNSCC primarily located in oropharynx,oral cavity, hypopharynx, or larynx, which is considered incurable by localtherapies.

5. Participants with oropharyngeal cancer must have results from testing of humanpapillomavirus HPV status.

6. No prior systemic treatment for R/M HNSCC.

7. At least one measurable noncerebral lesion according to RECIST 1.1.

8. PD-L1 positive (CPS ≥ 1).

9. Has adequate organ function.

10. All subjects of reproductive potential must agree to use an effective method ofcontraception, as determined by the Investigator, during and for 120 days after thelast dose of study treatment.

11. Able to to comply with all requirements of study participation (including all studyprocedures).

Exclusion Criteria:

1. Has squamous cell carcinoma of the primary site, such as nasopharynx, nasal cavity,sinuses, salivary glands, thyroid or parathyroid, skin, or of unknown primaryorigin.

2. Had other malignant tumors within the 5 years prior to enrollment.

3. Has a significant risk of bleeding assessed by the investigator based on imaging.

4. Radiologically documented evidence of major blood vessel invasion or tumor invadingorgans or there is a risk of esophagotracheal or esophagopleural fistula, or majorblood vessel encasement that the investigator determines will pose a significantlyincreased risk of bleeding.

5. Has known active central nervous system (CNS) metastases.

6. Has pleural effusion, pericardial effusion, or ascites with clinical symptoms orrequiring repeated drainage.

7. Previously received immunotherapy, including immune checkpoint inhibitors, immunecheckpoint agonists, immune cell therapy, and any other treatments targeting theimmune mechanisms of tumors.

8. Previously received radiation therapy for head or neck within 8 weeks prior toenrollment, received palliative radiation therapy for non-head or non-neck within 3weeks prior to enrollment.

9. Has a history severe bleeding tendency or coagulation dysfunction.

10. Has a history myocarditis, cardiomyopathy, and malignant arrhythmia.

11. Has a history arterial or venous thromboembolism events, transient ischemic attacks,cerebrovascular accidents, hypertensive crises, or hypertensive encephalopathyoccurred within 6 months prior to enrollment.

12. Pregnant or lactating female.