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

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)

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].

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: AK117 in combination with AK112; Drug: Placebo in combination with Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wenting Li; Phone Number: 18116403289; Email: wenting01.li@akesobio.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Kunyu Yang
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: lei Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK117 in combination with AK112	Drug: AK117 in combination with AK112; Following a predefined dose and date.
Active Comparator: Placebo in combination with Pembrolizumab	Drug: Placebo in combination with Pembrolizumab; Following a predefined dose and date.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression (per RECIST v1.1 criteria) assessed by investigators or death due to any cause, whichever occurs first.	Up to approximately 2 years
Objective Response Rate (ORR)	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , assessed by investigators based on RECIST v1.1.	Up to approximately 2 years
Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 2 years
Cmax	Maximum plasma concentration of AK112 and AK117 after administration.	Up to approximately 2 years
Cmin	Minimum plasma concentration of AK112 and AK117 after administration.	Up to approximately 2 years
Anti-drug antibodies (ADA)	Number of subjects with detectable ADA.	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: August 29, 2024
• First Submitted That Met QC Criteria: September 14, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: AK117-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No