Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy and safety of tislelizumab and tislelizumab in combination with investigational agent(s) in first-line recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Detailed Description
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This study will test whether tislelizumab alone and combined with other investigational agents can be used to improve treatment outcomes in participants with head and neck squamous cell carcinoma. The main goals of the study are to determine how many participants may no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment and to determine what adverse events, or side effects, participants might experience. Tislelizumab is used to block the programmed cell death protein-1 pathway so that immune system cells (T-cells) can better protect the body from infection and find tumor cells to attack. Tislelizumab may be used in combination with other therapies as a promising approach with potential therapeutic benefits to treat participants with cancer. The study will enroll approximately 160 participants. Participants will be randomly assigned (by chance, similar to flipping a coin) to one of the various treatment groups. Tislelizumab and investigational agents will be administered as an infusion through a vein at regularly scheduled intervals. The study will take place at multiple centers worldwide. Treatments will continue until participants experience no benefits, too many side effects, or withdraw consent.

Official Title
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A Randomized, Phase 2, Open-Label, Multi-Arm Study of Tislelizumab in Combination With Investigational Agents as First-Line Treatment in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: BGB-A425
* Drug: LBL-007


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx Participants should not have had prior systemic therapy administered in the R/M setting; systemic therapy which was completed prior to randomization/enrollment if given as part of multimodal treatment for locally or locoregionally advanced disease is allowed Participants must have positive PD-L1 expression (Combined Positive Score [CPS] ≥ 1) Have at least 1 measurable lesion as defined per RECIST v1.1 Eastern Cooperative Oncology Group Performance Status of 0 or 1 Adequate hematologic and organ function as indicated by specific laboratory values within 7 days of first dose of study drug Willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s) Exclusion Criteria: Recurrent or metastatic carcinoma of the nasopharynx (any histology), squamous cell carcinoma of unknown primary, squamous cell carcinoma that originated from the skin and salivary gland primary tumor or non-squamous histologies (eg, mucosal melanoma) Prior therapy with an anti-PD-1, anti-PD-L1, PD-L2, T-cell immunoglobulin and mucin domain containing-3 (TIM-3), LAG-3, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways Any active malignancy ≤ 2 years before randomization/enrollment except for the specific cancer under investigation in this study, those with a negligible risk of metastasis or death, and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, localized prostate cancer, and carcinoma in situ of the cervix or breast) History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, and acute lung diseases A history of severe hypersensitivity reactions to other monoclonal antibodies or has experienced a severe immune-mediated adverse event (imAE), an imAE that led to treatment discontinuation, or a cardiac or ocular imAE of any grade with prior immunotherapy Note: Other inclusion and exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tislelizumab<br>Tislelizumab 200 milligrams (mg) administered once every 3 weeks | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|
| Experimental: Tislelizumab + BGB-A425<br>Tislelizumab 200 mg administered once every 3 weeks with BGB-A425 | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;Drug: BGB-A425<br>* Administered intravenously<br>|
| Experimental: Tislelizumab + LBL-007<br>Tislelizumab 200 mg administered once every 3 weeks with LBL-007 | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;Drug: LBL-007<br>* Administered intravenously<br>|
| Experimental: Tislelizumab + BGB-A425 + LBL-007<br>Tislelizumab 200 mg administered once every 3 weeks with BGB-A425 and LBL-007 | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;Drug: BGB-A425<br>* Administered intravenously<br>Drug: LBL-007<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as percentage of participants who have a confirmed complete response (CR) or a confirmed partial response (PR) as assessed by the investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Up to approximately 3 years and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease assessed by the investigators per RECIST v1.1 or death, whichever occurs first | Up to approximately 3 years and 6 months | 
| Duration of Response (DOR) | DOR is defined as the time from the first determination of a confirmed response per RECIST v1.1 until the first documentation of progression or death, whichever occurs first | Up to approximately 3 years and 6 months | 
| Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants with a best overall response of a confirmed CR, a confirmed PR, or a durable stable disease (SD) (SD duration ≥ 24 weeks) | Up to approximately 3 years and 6 months | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants with a best overall response of a confirmed CR, a confirmed PR, or SD | Up to approximately 3 years and 6 months | 
| Number of Participants with Adverse Events | Number of participants with adverse events, including laboratory values, vital signs, physical examinations, and electrocardiogram findings | Up to approximately 3 years and 6 months | 
| Overall Survival (OS) | OS is defined as the time from the date of randomization to the date of death due to any cause | Up to approximately 3 years and 6 months | 
| Number of Participants with Anti-Drug Antibodies (ADAs) | Number of participants with detectable ADAs | Up to approximately 3 years and 6 months |