Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
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
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.
Interventions
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies 1. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx 2. 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 programmed cell death protein ligand-1 (PD-L1) expression (Combined Positive Score \[CPS\] ≥ 1) * Have at least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (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-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, anti-programmed cell death ligand-2 (PD-L2), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 21.2 months | 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. Complete response is defined as disappearance of all target lesions, disappearance of all nontarget lesions and normalization of tumor marker level, and no new lesions. Partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, no unequivocal progression of non-target lesions, and no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 21.2 months | PFS is defined as the time from the date of randomization to the date of the first documentation of progressive disease (PD) assessed by the investigators per RECIST v1.1 or death, whichever occurred first. PD is defined as at least a 20% increase in the sum of diameters of target lesions, unequivocal progression of existing non-target lesions, or new lesions. |
| Duration of Response (DOR) | Up to 21.2 months | 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 occurred first. |
| Clinical Benefit Rate (CBR) | Up to 21.2 months | CBR is defined as the percentage of participants with a best overall response of a confirmed CR, a confirmed PR, or durable stable disease (SD) (SD duration ≥ 24 weeks). SD is defined as neither sufficient decrease in size of target lesions to qualify for PR nor sufficient increase to qualify for PD, no progressive disease in nontarget lesions, and no new lesions. |
| Disease Control Rate (DCR) | Up to 21.2 months | DCR is defined as the percentage of participants with a best overall response of a confirmed CR, a confirmed PR, or SD. |
| Number of Participants With Treatment-Emergent Adverse Events | From first dose to 30 days after last dose, maximum treatment duration was 19.3 months. | Number of participants with adverse events (AEs), including laboratory values, vital signs, physical examinations, and electrocardiogram findings. AEs were graded on a scale of Grade 1 to Grade 5, with Grade 1 being least severe and Grade 5 being most severe. An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether considered related to study drug or not. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was considered a significant medical AE by the investigator based on medical judgement. |
| Overall Survival (OS) | Up to 21.2 months | OS is defined as the time from the date of randomization to the date of death due to any cause. |
Countries
Australia, Canada, China, France, Georgia, Italy, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
BeiGene
Participant flow
Recruitment details
Participants were enrolled at 57 centers in 13 countries globally. The main part of the study completed on 17 June 2025. At that time, participants who continued to receive clinical benefit were offered continued access to study treatment in the Extended Access Period. Results are reported up to the data cut-off date of 17 June 2025.
Pre-assignment details
Eligible participants were randomized in a 1:1 ratio into the four treatment groups. Randomization was stratified based on programmed cell death protein ligand-1 (PD-L1) expression.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants |
| Age, Continuous | 62.8 years STANDARD_DEVIATION 11.06 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Missing | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 151 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 23 Participants |
| Race/Ethnicity, Customized Race Missing | 1 Participants |
| Race/Ethnicity, Customized Race Not Reported | 1 Participants |
| Race/Ethnicity, Customized Race White | 9 Participants |
| Region of Enrollment Australia | 1 participants |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment China | 46 participants |
| Region of Enrollment France | 2 participants |
| Region of Enrollment Georgia | 4 participants |
| Region of Enrollment Italy | 7 participants |
| Region of Enrollment South Korea | 5 participants |
| Region of Enrollment Spain | 1 participants |
| Region of Enrollment Taiwan | 7 participants |
| Region of Enrollment Thailand | 2 participants |
| Region of Enrollment Turkey (Türkiye) | 1 participants |
| Region of Enrollment United Kingdom | 0 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 19 / 40 | 16 / 40 | 20 / 40 | 19 / 40 |
| other Total, other adverse events | 36 / 40 | 32 / 39 | 37 / 40 | 39 / 40 |
| serious Total, serious adverse events | 17 / 40 | 14 / 39 | 11 / 40 | 16 / 40 |
Outcome results
None listed