Overview

This is a phase 3 study. All subjects arerecurrent or metastatic head and neck squamous Cell Carcinoma (R/M HNSCC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 combined with AK117 versus pembrolizumab combined with placebo in patients with R/M HNSCC whose tumors have programmed cell death-ligand 1 (PD-L1) positive [Combined Positive Score (CPS) greater than or equal to 1].

Eligibility

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 local therapies.
5. Participants with oropharyngeal cancer must have results from testing of human papillomavirus 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 of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
11. Able to to comply with all requirements of study participation (including all study procedures).

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 primary origin.
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 invading organs or there is a risk of esophagotracheal or esophagopleural fistula, or major blood vessel encasement that the investigator determines will pose a significantly increased risk of bleeding.
5. Has known active central nervous system (CNS) metastases.
6. Has pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage.
7. Previously received immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, and any other treatments targeting the immune mechanisms of tumors.
8. Previously received radiation therapy for head or neck within 8 weeks prior to enrollment, received palliative radiation therapy for non-head or non-neck within 3 weeks 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 encephalopathy occurred within 6 months prior to enrollment.
12. Pregnant or lactating female.