Clinical trial NCT06601335: A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
Official title: A Randomized, Controlled, Multicenter Phase 3 Study of AK112 in Combination With AK117 Versus Pembrolizumab as First Line Treatment for a Programmed Cell Death-ligand 1 (PD-L1) Positive Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
measure: Adverse Events (AEs)
timeFrame: Up to approximately 2 years
measure: Cmax
timeFrame: Up to approximately 2 years
measure: Cmin
timeFrame: Up to approximately 2 years
measure: Anti-drug antibodies (ADA)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References: