A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer (SKYSCRAPER-04)

A Phase II, Safety, and Efficacy Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Patients With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer

The purpose of this study is to evaluate the efficacy and safety of tiragolumab in combination with atezolizumab and atezolizumab monotherapy in patients with programmed death-ligand 1 (PD-L1)-positive cervical cancer (metastatic and/or recurrent).

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Tiragolumab; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Limited
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-070
      • Hospital Araujo Jorge
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • Hospital de Caridade de Ijui
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01317-000
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Glen Site
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
  • San José, Costa Rica, 10108
    • ICIMED Instituto de Investigación en Ciencias Médicas
• France
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Montpellier, France, 34298
    • Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
  • Saint-Herblain, France, 44805
    • Ico - Site René Gauducheau
  • Villejuif, France, 94800
    • Gustave Roussy
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Tumori Napoli
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
  • Lombardy
    • Milan, Lombardy, Italy, 20141
      • Istituto Europeo di Oncologia
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64570
      • Christus Muguerza Clinica Vidriera
• Panama
  • Panama City, Panama, 0832
    • The Panama Clinic
  • Panama City, Panama, 0801
    • Centro Oncológico de Panamá
• Peru
  • San Isidro, Peru, Lima 27
    • Clinica Ricardo Palma
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologi
  • Gdynia, Poland, 81-519
    • Szpital Morski im.PCK
  • Gliwice, Poland, 44-101
    • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
• Russia
  • Tomsk, Russia, 634050
    • Tomsk scientific research institute of oncology SO RAMN, PAD
  • Volgograd, Russia, 400138
    • Volgograd Regional Clinical Oncology Dispensary
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 143422
      • MEDSI Clinical Hospital on Pyatnitsky Highway
  • Sverdlovsk Oblast
    • Chelyabinsk, Sverdlovsk Oblast, Russia, 454087
      • Chelyabisnk regional clinical center for oncology and nuclear medicine
  • Tatarstan Republic
    • Kazan', Tatarstan Republic, Russia, 420029
      • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
• South Korea
  • Daegu, South Korea, 41931
    • Keimyung University Dongsan Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 06273
    • Gangnam Severance Hospital
  • Seoul, South Korea, 01812
    • Korea Cancer Center Hospital of Korea Institute of Radiological and Medical Sciences
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 110
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation, Linkou Branch
• Thailand
  • Muang, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, NW1 - 2PG
    • University College London Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates
  • California
    • Irvine, California, United States, 92616
      • Kaiser Permanente - Irvine
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oncology Associates of Oregon, P.C

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix after progression on or after 1-2 lines of prior systemic chemotherapy in the metastatic/recurrent setting that is not amenable to curative treatment with systemic chemotherapy, surgery, and/or radiotherapy
• Radiologically-measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1
• Cervical cancer tissue for study analysis (archival or fresh biopsy specimen)
• Life expectancy of at least 12 weeks
• Adequate hematologic and organ function
• Female of childbearing potential must be willing to comply with adequate contraception

Exclusion Criteria:

• Treatment with investigational therapy with therapeutic intent within 28 days prior to randomization
• Active or untreated central nervous system (CNS) or brain metastases
• Active or history of autoimmune disease or immune deficiency
• Active tuberculosis
• Known, clinically significant liver disease
• Severe infection per investigator judgement at the time of randomization or any active infection that, in the opinion of the investigator, could impact patient safety
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to randomization
• Treatment with systemic immunosuppressive medications within 1 week prior to randomization or anticipation of need for systemic immunosuppressive medication during study
• Pregnant or breastfeeding woman
• Known hypersensitivity to any component of the tiragolumab or atezolizumab formulations

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiragolumab plus Atezolizumab; Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Drug: Tiragolumab; Tiragolumab at a fixed dose of 600 milligrams (mg) will be administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.; Other Names: RO7092284; Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; RO5541267
Experimental: Atezolizumab; Participants will receive atezolizumab monotherapy until unacceptable toxicity or loss of clinical benefit as determined by the investigator.	Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; RO5541267

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-crossover Period: Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥4 weeks apart, as determined by the IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR=Disappearance of all target & non-target lesions or any pathological lymph nodes (whether target or non-target) have reduction in short axis to <10 millimeters (mm). PR=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. The study enrolled participants with measurable disease as determined by the investigator. Participants found to have non-measurable disease at baseline according to RECIST v1.1 (through IRC assessment or Protocol Deviations) were only considered responders if they achieved a CR. Percentages have been rounded off.	From randomization up to approximately 17 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre- and Post-crossover Periods: Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be 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.	Up to approximately 50.3 months
Pre-crossover Period: IRC-assessed Duration of Response (DOR)	DOR was defined for participants who had objective response (OR) as time from first occurrence of a documented OR (CR/PR) to date of PD or death from any cause (whichever occurred first), determined by IRC per RECIST v1.1. CR=Disappearance of all target & non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to <10 mm. PR=≥30% decrease in SOD of all target lesions, taking as reference baseline SOD, in absence of CR. PD = ≥ 20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Study enrolled participants with measurable disease as per investigator. Participants who had non-measurable disease at baseline according to RECIST v1.1 (IRC assessment or Protocol Deviations) were only considered responders if they achieved CR.	First occurrence of a documented objective response to the date of PD or death from any cause, whichever occurred first (up to approximately 17 months)
Pre-crossover Period: IRC-assessed Disease Control Rate (DCR)	DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD), as determined by the IRC according to RECIST v1.1. CR and PR were defined the same as in the description of primary outcome measure (OM), ORR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD = ≥ 20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Study enrolled participants with measurable disease as per the investigator. Participants who had non-measurable disease at baseline per RECIST v1.1 (IRC assessment or Protocol Deviations) were only considered responders if they achieved CR.	From randomization up to approximately 17 months
Pre-crossover Period: Investigator-assessed Best Clinical Response (BCR) Rate	BCR was defined as the percentage of participants with a CR, PR, or SD, as determined by the investigator according to RECIST v1.1. CR=Disappearance of all target & non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to <10 mm. PR=At least a 30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD=At least 20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline); in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s). Percentages have been rounded off.	From randomization up to approximately 17 months
Pre-crossover Period: Investigator-assessed Duration of BCR	Duration of BCR was defined for BCR responders as the time from first occurrence of a documented response (CR, PR, or SD) to date of PD or death from any cause (whichever occurred first), as clinically determined by the investigator according to RECIST v1.1. CR=Disappearance of all target & non-target lesions or any pathological lymph nodes (whether target/non-target) have reduction in short axis to <10 mm. PR = ≥30% decrease in SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. SD=Neither sufficient shrinkage to qualify for CR/PR nor sufficient increase to qualify for PD. Participants were classified as SD only if SD was observed on two consecutive assessments ≥6 weeks apart. PD = ≥20% increase in SOD of target lesions, taking as reference smallest SOD at prior timepoints (including baseline); in addition to relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s).	First occurrence of a documented clinical response to the date of PD or death from any cause, whichever occurred first (up to approximately 17 months)
Pre-crossover Period: IRC-assessed Progression-free Survival (PFS)	PFS was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first), as determined by the IRC according to RECIST v1.1. PD was defined as at least 20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline); in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s).	From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 17 months)
Pre-crossover Period: IRC-assessed PFS Rate at 6 Months	PFS rate was defined as the percentage of participants who were event-free at 6 months post-randomization, as determined by the IRC according to RECIST v1.1. PFS was defined as the time from randomization to the first occurrence of PD or death from any cause (whichever occurred first), as determined by the IRC according to RECIST v1.1. PD was defined as at least 20% increase in SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline); in addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm or unequivocal progression in non-target lesion(s)..	At Month 6
Pre-crossover Period: Overall Survival (OS)	OS was defined as the time of randomization to death from any cause.	From randomization to death from any cause (up to approximately 17 months)
Pre-crossover Period: OS Rate at 6 Months and 12 Months	OS rate was defined as the percentage of participants who were still alive at 6 months and 12 months. OS was defined as the time of randomization to death from any cause.	At Months 6 and 12
Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab		Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days)
Pre-crossover Period: Maximum Serum Concentration (Cmax) of Tiragolumab		At 30 minutes post-dose on Cycle 1 Day 1 (1 Cycle = 21 days)
Pre-crossover Period: Cmin of Atezolizumab		Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days)
Pre-crossover Period: Cmax of Atezolizumab		At 30 minutes post-dose on Day 1 of Cycle 1 (1 cycle = 21 days)
Pre-crossover Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab	Participants were considered treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titre units[t.u]) than the titre of the baseline sample (treatment-enhanced ADA response).	Up to approximately 17 months
Pre-crossover Period: Percentage of Participants With ADAs to Atezolizumab	Participants were considered treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 t.u) than the titre of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.	Up to approximately 17 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum Serum Concentration (Cmin) of Tiragolumab		Pre dose: Day 1 of Cycles 2, 3, 4, 8, 12 and 16
Maximum Serum Concentration (Cmax) of Tiragolumab		Cycle 1 Day 1 at 30 minutes post-dose
Cmin of Atezolizumab		Pre dose: Day 1 of Cycles 2, 3, 4, 8, 12 and 16
Cmax of Atezolizumab		Day 1 of Cycle 1 at 30 minutes post-dose
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab	Participants were classified as treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titre units) than the titre of the baseline sample (treatment-enhanced ADA response).	Predose on Day 1 of Cycles (each cycle is 21 days) 1, 2, 3, 4, 8, 12 and 16
Percentage of Participants With ADAs to Atezolizumab	Participants were classified as treatment-emergent ADA-positive if they were ADA negative at baseline or missing data but developed an ADA response following study drug administration (treatment-induced ADA response) or if they were ADA-positive at baseline and the titre of one or more post-baseline samples was at least 4-fold greater (i.e., ≥ 0.60 titre units) than the titre of the baseline sample (treatment-enhanced ADA response).	Predose on Day 1 of Cycles (each cycle is 21 days) 1, 2, 3, 4, 8, 12 and 16

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Salani R, McCormack M, Kim YM, Ghamande S, Hall SL, Lorusso D, Barraclough L, Gilbert L, Guzman Ramirez A, Lu CH, Sabatier R, Colombo N, Hu Y, Krishnan V, Molinero L, Feng Y, Kim N, Castro M, Lin YG, Monk BJ. A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04). Int J Gynecol Cancer. 2024 Aug 5;34(8):1140-1148. doi: 10.1136/ijgc-2024-005588.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Actual): December 8, 2021
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: February 19, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab; Tiragolumab
• Other Study ID Numbers: WO42017; 2019-004895-21 (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