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: Active, not recruiting
• 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 Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Praha 5, Czechia, 150 06
    • Fakultni nemocnice v Motole; Onkologicka klinika 2. LF UK a FN Motol
• France
  • Caen, France, 14076
    • Centre Francois Baclesse; Oncologie
  • Lyon, France, 69373
    • Centre Leon Berard; Departement Oncologie Medicale
  • Montpellier, France, 34298
    • Institut régional du Cancer Montpellier
  • Paris, France, 75231
    • Institut Curie; Oncologie Medicale
  • Pessac, France, 33604
    • CHU Bordeaux
  • Vandoeuvre-Les-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine
• Greece
  • Athens, Greece, 115 22
    • Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
  • Athens, Greece, 12462
    • Attiko Hospital University of Athens; 2Nd Dept. of Propaedeutic Medicine
  • Heraklion, Greece, 711 10
    • Periph. University General Hospital of Heraklion Crete; Oncology Department
  • Thessaloniki, Greece, 546 45
    • Euromedical General Clinic of Thessaloniki; Oncology Department
• Hungary
  • Gy?r, Hungary, 9024
    • Gy?r-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház
  • Pécs, Hungary, 7623
    • Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
• Italy
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • ASST degli Spedali Civili di Brescia
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori;S.S. Trattamento MedicoTumori dellaTesta e delCollo
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital NZ
  • Tauranga, New Zealand, 3112
    • Tauranga Hospital, Clinical Trials Unit; BOP Clinical School
  • Wellington, New Zealand, 6002
    • Wellington Hospital
• Poland
  • ?ód?, Poland, 90-338
    • Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna
  • Bielsko- Biala, Poland, 43-300
    • Beskidzkie Centrum Onkologii- Szpital Miejski
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
  • Lublin, Poland, 20-090
    • CENTRUM ONKOLOGII ZIEMI LUBELSKIEJ IM. ?W. JANA Z DUKLI; II Oddzia? Onkologii Klinicznej
  • Poznan, Poland
    • Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzia? Onkologii Klinicznej i Doswiadczalnej
• Spain
  • Barcelona, Spain, 08908
    • Institut Catala d Oncologia Hospital Duran i Reynals
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe; Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital;Oncology and Hematology Office Critical Care Center, 14H
  • Taipei City, Taiwan, 112201
    • Taipei Veterans General Hospital; Department of Oncology
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital; Oncology
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology
• 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
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Fulham
  • 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, 21231
      • Johns Hopkins Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center; Oncology

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	Time Frame
Confirmed Objective Response Rate (ORR)	Up to approximately 43 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Up to approximately 43 months
Progression-Free Survival (PFS)	Up to approximately 43 months
Overall Survival (OS)	Up to approximately 43 months
Progression-Free Survival Rate at 6 Months	Month 6
Overall Survival Rate at 6 Months and 12 Months	Month 6, Month 12
Time to Confirmed Deterioration (TTCD) in Patient-Reported Physical Functioning	Up to approximately 43 months
Percentage of Participants With Adverse Events (AEs)	Up to approximately 43 months
Minimum Serum Concentration (Cmin) of Atezolizumab	Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months
Maximum Serum Concentration (Cmax) of Atezolizumab	Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months
Cmin of Tiragolumab	Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months
Cmax of Tiragolumab	Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab	From baseline up to approximately 43 months
Number of Participants With ADAs to Tiragolumab	From baseline up to approximately 43 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 (Estimated): October 2, 2024

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): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• 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: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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