A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck (SKYSCRAPER-09)

A Phase II, Randomized, Double Blind Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Patients With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Drug: Atezolizumab; Drug: Tiragolumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 656 53
    • Masarykuv onkologicky ustav
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Prague, Czechia, 150 06
    • Fakultni nemocnice v Motole
• France
  • Bordeaux, France, 33075
    • CHU Bordeaux
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Lyon, France, 69373
    • Centre Leon Berard
  • Montpellier, France, 34298
    • Institut régional du Cancer Montpellier
  • Paris, France, 75231
    • Institut Curie
  • Vandœuvre-lès-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine
• Greece
  • Athens, Greece, 115 22
    • Anticancer Hospital Ag Savas
  • Athens, Greece, 12462
    • Attiko Hospital University of Athens
  • Heraklion, Greece, 711 10
    • Periph. University General Hospital of Heraklion Crete
  • Thessaloniki, Greece, 546 45
    • Euromedical General Clinic of Thessaloniki
• Hungary
  • Gy?r, Hungary, 9024
    • Gy?r-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház
  • Kecskemét, Hungary, 6000
    • Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem
• Italy
  • Lombardy
    • Brescia, Lombardy, Italy, 25100
      • ASST degli Spedali Civili di Brescia
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
• Poland
  • Bielsko-Biala, Poland, 43-300
    • Beskidzkie Centrum Onkologii- Szpital Miejski
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Lodz, Poland, 90-242
    • Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
  • Lublin, Poland, 20-090
    • Centrum Onkologii Ziemi Lubelskiej Im. ?W. Jana Z Dukli
  • Poznan, Poland
    • Uniwersytecki Szpital Kliniczny w Poznaniu
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Taipei, Taiwan, 112201
    • Taipei Veterans General Hospital
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego Health
    • Los Angeles, California, United States, 90095
      • UCLA
  • Florida
    • Tallahassee, Florida, United States, 32308
      • SCRI Florida Cancer Specialists PAN
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Atezolizumab + Tiragolumab; Participants will receive atezolizumab followed by tiragolumab every three weeks (Q3W) on Day 1 of each 21-day cycle.	Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; RO5541267; Drug: Tiragolumab; Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: RO7092284
Placebo Comparator: Atezolizumab + Placebo; Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle.	Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; RO5541267; Drug: Placebo; Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to approximately 30.6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	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.	From first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 30.6 months)
Progression-free Survival (PFS)	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.	From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 30.6 months)
Overall Survival (OS)	OS was defined as the time from randomization to death from any cause. K-M method was used to estimate the median OS.	From randomization to death from any cause (up to approximately 30.6 months)
PFS Rate at 6 Months	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.	Month 6
OS Rate at 6 Months and 12 Months	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.	Months 6 and 12
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	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.	Up to approximately 30.6 months
Number of Participants With Adverse Events (AEs)	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.	From study start up to 90 days after last dose (up to approximately 52.9 months)
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	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).	Up to approximately 49.9 months
Number of Participants With ADAs to Tiragolumab	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).	Up to approximately 49.9 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2021
• Primary Completion (Actual): September 20, 2023
• Study Completion (Actual): August 27, 2025

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

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; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab; Tiragolumab
• Other Study ID Numbers: BO42533; 2020-002852-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No