A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer
- Registration Number
- NCT04300647
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 172
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab Atezolizumab Participants will receive atezolizumab monotherapy until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Tiragolumab plus Atezolizumab Tiragolumab Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Tiragolumab plus Atezolizumab Atezolizumab Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
- Primary Outcome Measures
Name Time Method Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR) From randomization up to approximately 17 months ORR is 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 lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The study enrolled patients 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events Up to 36 months An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
IRC-Assessed Duration of Response (DOR) First occurrence of a documented objective response to the date of disease progression or death from any cause, whichever occurs first (up to approximately 17 months) DOR is defined for participants who had an objective response as the time from the first occurrence of a documented objective response (CR or PR) to the date of progressive disease (PD) or death from any cause (whichever occurred first), as determined by the IRC according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline). The study enrolled patients 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.
IRC-Assessed Disease Control Rate (DCR) From randomization up to approximately 17 months Disease control rate is 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: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD: neither sufficient shrinkage to qualify for CR or 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. The study enrolled patients 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.
Investigator-Assessed Best Clinical Response (BCR) Rate From randomization up to approximately 17 months BCR is defined as the percentage of participants with a CR, PR, or SD, as determined by the investigator. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD: neither sufficient shrinkage to qualify for CR or 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.
Investigator-Assessed Duration of BCR First occurrence of a documented clinical response to the date of disease progression or death from any cause, whichever occurs first (up to approximately 17 months) Duration of BCR is defined for BCR responders as the time from the first occurrence of a documented response (CR, PR, or SD) to the 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 lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD: neither sufficient shrinkage to qualify for CR or 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 a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
IRC-Assessed Progression-Free Survival (PFS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 17 months) PFS is 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: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline).
IRC-Assessed PFS Rate at 6 Months 6 months PFS rate is defined as the percentage of participants that were event free, as determined by the IRC according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline).
Overall Survival (OS) From randomization to death from any cause (up to approximately 17 months) OS is defined as the time of randomization to death from any cause.
OS Rate at 6 Months and 12 Months 6 months, 12 months Reported here are the percentages of participants who were still alive at 6 months and 12 months.
Trial Locations
- Locations (56)
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Lazio, Italy
Centro Oncológico de Panamá
🇵🇦Panama, Panama
The Panama Clinic
🇵🇦Panama, Panama
Clinica Ricardo Palma
🇵🇪San Isidro, Peru
Szpital Morski im.PCK
🇵🇱Gdynia, Poland
Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice
🇵🇱Gliwice, Poland
Wielkopolskie Centrum Onkologii im. M. Sklodowskiej-Curie
🇵🇱Poznan, Poland
Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Maharaj Nakorn Chiang Mai Hospital
🇹ðŸ‡Muang, Thailand
University College London Hospital
🇬🇧London, United Kingdom
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Oncology Associates of Oregon, P.C
🇺🇸Eugene, Oregon, United States
Clinica CIMCA
🇨🇷San José, Costa Rica
ICIMED Instituto de Investigación en Ciencias Médicas
🇨🇷San José, Costa Rica
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
🇫🇷Montpellier, France
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
Gustave Roussy
🇫🇷Villejuif CEDEX, France
Istituto Tumori Napoli
🇮🇹Napoli, Campania, Italy
Arizona Oncology Associates
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente - Irvine
🇺🇸Irvine, California, United States
Augusta University
🇺🇸Augusta, Georgia, United States
MEDSI Clinical Hospital on Pyatnitsky Highway
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Mater Misericordiae Limited
🇦🇺South Brisbane, Queensland, Australia
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Hospital Araujo Jorge
🇧🇷Goiania, Goiás, Brazil
Hospital de Caridade de Ijui
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, São Paulo, Brazil
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
London Regional Cancer Centre
🇨🇦London, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre - Glen Site
🇨🇦Montreal, Quebec, Canada
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Korea Cancer Center Hospital of Korea Institute of Radiological and Medical Sciences
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Christus Muguerza Clinica Vidriera
🇲🇽Monterrey, Nuevo LEON, Mexico
Chelyabisnk regional clinical center for oncology and nuclear medicine
🇷🇺Chelyabinsk, Sverdlovsk, Russian Federation
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Tatarstan, Russian Federation
Tomsk scientific research institute of oncology SO RAMN, PAD
🇷🇺Tomsk, Russian Federation
Volgograd Regional Clinical Oncology Dispensary
🇷🇺Volgograd, Russian Federation
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸La Coruna, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei City, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Medical Foundation, Linkou Branch
🇨🇳Taoyuan City, Taiwan