Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.
Interventions
DRUGAtezolizumab
Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.
DRUGTiragolumab
Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
DRUGPlacebo
Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically or cytologically confirmed recurrent/metastatic SCCHN involving the oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local therapies * Known results from human papillomavirus (HPV) status test for oropharyngeal carcinoma * No prior systemic therapy for metastatic and/or recurrent SCCHN * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 * Tumor PD-L1 expression as determined by PD-L1 immunohistochemistry assay * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Life expectancy \>=12 weeks Key
Exclusion criteria
* Disease suitable for local therapy with curative intent * Progressive or recurrent disease within 6 months of the last dose of curative intent systemic treatment for locally advanced SCCHN * Rapidly progressing disease in the opinion of the treating investigator * Grade \>=2 unresolved toxicity related to surgery or other prior therapies * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * History of additional malignancy other than SCCHN within 5 years prior to randomization * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1 therapeutic antibodies * Treatment with systemic immunostimulatory agents or systemic immunosuppressive medication * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed Objective Response, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to approximately 30.6 months | A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | From first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 30.6 months) | DOR was defined as the time from the first occurrence of a documented confirmed OR to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. Confirmed OR was defined as either a CR or a PR on 2 consecutive occasions ≥ 4 weeks apart. CR was defined as disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate the median DOR. |
| Progression-free Survival (PFS) | From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 30.6 months) | PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the median PFS. |
| Overall Survival (OS) | From randomization to death from any cause (up to approximately 30.6 months) | OS was defined as the time from randomization to death from any cause. K-M method was used to estimate the median OS. |
| PFS Rate at 6 Months | Month 6 | PFS rate at 6 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at Month 6. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate the PFS rate. Percentages have been rounded off. |
| OS Rate at 6 Months and 12 Months | Months 6 and 12 | OS rate at 6 months and 12 months was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off. |
| Time to Confirmed Deterioration (TTCD) in Participant-reported Physical Functioning (PF), as Measured by the Patient-reported Outcomes Measurement Information System (PROMIS) Item Bank Version 2.0 (v2.0)-PF-Short Form 10b | Up to approximately 30.6 months | TTCD=time from the date of randomization to the first confirmed clinically meaningful deterioration (CCMD). PROMIS Item Bank v2.0-PF- Short Form 10b is a 10-item participant-reported questionnaire including 2 types of items to assess PF: 6 ability-based items assessing difficulty in performing activities, scored on a 5-point scale ranging from 1=Unable to do, 2=With much difficulty, 3=With some difficulty, 4=With a little difficulty, 5=Without any difficulty; and 4 limitation-based items assessing the extent to which health limits activities, scored on a 5-point scale ranging from 1=Cannot do, 2=Quite a lot, 3=Somewhat, 4=Very little, 5=Not at all. Item responses were summed to generate a raw score and converted to a PROMIS T-score, with a higher T-score indicating better PF. CCMD=decrease from baseline (≥ 4 points) in T-score, held for at least 2 consecutive assessments. K-M method was used to estimate median TTCD. |
| Number of Participants With Adverse Events (AEs) | From study start up to 90 days after last dose (up to approximately 52.9 months) | An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE was therefore any of the following: Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Serum Concentration of Atezolizumab at Specified Timepoints | Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/early discontinuation (ED) (1 Cycle=21 days) (up to approximately 49.9 months) | — |
| Serum Concentration of Tiragolumab at Specified Timepoints | Pre-dose and 30 minutes post-dose on Day 1 of Cycle 1; Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, & 16; and at treatment completion/ED (1 Cycle=21 days) (up to approximately 49.9 months) | — |
| Number of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab | Up to approximately 49.9 months | Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following atezolizumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 titer unit (t.u.) greater than the baseline titer result (treatment-enhanced ADA response). |
| Number of Participants With ADAs to Tiragolumab | Up to approximately 49.9 months | Participants were considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following tiragolumab administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was greater than the titer of the baseline sample by a scientifically reasonable margin such as at least 0.60 t.u. greater than the baseline titer result (treatment-enhanced ADA response). |
Countries
Czechia, France, Greece, Hungary, Italy, New Zealand, Poland, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 123 participants diagnosed with recurrent/metastatic programmed death-ligand 1 (PD-L1) positive squamous cell carcinoma of the head and neck (SCCHN) took part in the study at 57 investigative sites across 13 countries from 02 March 2021 to 27 August 2025.
Pre-assignment details
Participants were randomized in a 2:1 ratio to receive either tiragolumab + atezolizumab (Tira + Atezo) or placebo + atezolizumab (Pbo + Atezo). The study is considered "Completed" because all the pre-planned study activities and analyses have been performed.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.7 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 31 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 28 / 39 | 62 / 80 |
| other Total, other adverse events | 28 / 39 | 68 / 80 |
| serious Total, serious adverse events | 14 / 39 | 23 / 80 |
Outcome results
None listed