Evaluation of Tislelizumab, LBL-007, and Surzebiclimab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

The primary objective of this study is to assess the **antitumor activity** of **tislelizumab** in combination with investigational agents in patients with recurrent or metastatic **Head and Neck Squamous Cell Carcinoma**. This evaluation is clinically relevant as it aims to determine the efficacy of this combination therapy as a first-line treatment, potentially offering a new therapeutic option for this patient population.

Secondary objectives include:

• To further assess the antitumor activity of tislelizumab plus investigational agent(s).
• To assess the safety and tolerability of tislelizumab plus investigational agent(s).
• To assess overall survival (OS).
• To assess host immunogenicity to tislelizumab and investigational protein therapeutics.

The clinical trial involves a total of **132 participants** diagnosed with **Head and Neck Squamous Cell Carcinoma**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including histologically or cytologically confirmed recurrent or metastatic carcinoma that is deemed incurable by local therapies. Eligible primary tumor locations include the oropharynx, oral cavity, hypopharynx, and larynx. Subjects must not have received prior systemic therapy in the recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is permissible. Participants are required to have a positive PD-L1 expression, at least one measurable lesion as per RECIST v1.1, and an Eastern Cooperative Oncology Group Performance Status of 0 or 1. Adequate hematologic and organ function is necessary, as indicated by specific laboratory values within seven days of the first dose of the study drug. Additionally, participants must be willing to use a highly effective method of birth control during the study and for at least 120 days after the last dose of the study drug(s). The trial includes a vulnerable population, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, Phase 2, open-label, multi-arm study designed to evaluate the antitumor activity of **tislelizumab** in combination with investigational agents as a first-line treatment for patients with recurrent or metastatic **head and neck squamous cell carcinoma** (HNSCC). The trial aims to assess the confirmed objective response rate (ORR) as the primary endpoint, with secondary endpoints including progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), disease control rate (DCR), overall survival (OS), and the incidence and severity of adverse events (AEs) according to NCI-CTCAE v5.0. The study will also evaluate immunogenic responses through the detection of anti-drug antibodies (ADA).

The trial is expected to commence recruitment on October 16, 2023, and is estimated to conclude by March 16, 2026. Participants will be involved in the study for a maximum treatment period of 24 months. The study involves multiple investigational products, including **LBL-007**, **BGB-A425**, and **tislelizumab**, all administered via **intravenous infusion**. The maximum daily dose for LBL-007 and BGB-A425 is 600 mg, while for tislelizumab, it is 200 mg. The total maximum dose for LBL-007 and BGB-A425 is 20.9 g, and for tislelizumab, it is 7 g.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically or cytologically confirmed recurrent or metastatic HNSCC, positive PD-L1 expression, and adequate hematologic and organ function. Participants must also have at least one measurable lesion as defined by RECIST v1.1 and an Eastern Cooperative Oncology Group Performance Status of 0 or 1. Follow-up visits will be conducted to monitor treatment response and safety, with assessments based on RECIST v1.1 and NCI-CTCAE v5.0 criteria. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. Additionally, failure to comply with study procedures or the emergence of any condition that, in the investigator's opinion, would make continued participation detrimental to the participant's health, may also lead to early termination. The trial is not categorized as low intervention and does not include pediatric subjects.

The clinical trial involves the administration of three investigational agents, each with specific pharmaceutical characteristics and administration protocols. **LBL-007** is provided as a **concentrate for solution for infusion**. The active substance, also named LBL-007, is a protein of other origin. The maximum daily dose is 600 mg, with a total maximum dose of 20.9 g over a treatment period of 24 weeks. The administration route is via **intravenous infusion**, and the formulation is not designed for pediatric use. Participant compliance will be monitored through regular assessments of infusion adherence and dosage accuracy.

**BGB-A425**, with the active substance **Surzebiclimab**, is administered as an **infusion**. This investigational agent is also a protein of other origin. The dosing schedule allows for a maximum daily dose of 600 mg and a total maximum dose of 20.9 g over a 24-week period. The administration is conducted through **intravenous infusion**. As with LBL-007, this formulation is not intended for pediatric populations, and compliance will be monitored similarly.

**Tislelizumab** is provided as a **concentrate for solution for infusion**. The active substance, Tislelizumab, is a protein of other origin. The maximum daily dose is set at 200 mg, with a total maximum dose of 7 g over the course of 24 weeks. The administration is performed via **intravenous infusion**. This formulation is also not suitable for pediatric use. Monitoring of participant compliance will be conducted through scheduled evaluations of infusion adherence and dosage administration.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The investigational agents are administered in accordance with the trial protocol, ensuring adherence to the specified dosing schedules and administration routes. Compliance monitoring is integral to the study, ensuring that participants receive the correct dosages and adhere to the treatment regimen as outlined in the clinical trial protocol.

The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the **Confirmed Objective Response Rate (ORR)**, which will be evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Secondary endpoints include **Progression-Free Survival (PFS)**, **Duration of Response (DOR)**, **Clinical Benefit Rate (CBR)**, and **Disease Control Rate (DCR)**, all assessed by the same criteria. Additionally, the trial will measure the incidence and severity of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) in both the reference arm (tislelizumab alone) and experimental arms (tislelizumab plus investigational agents). Other secondary endpoints include **Overall Survival (OS)** and immunogenic responses to tislelizumab and investigational protein therapeutics, evaluated through the detection of anti-drug antibodies (ADA).