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

Phase 2

Completed

Conditions: Cervical Cancer

Interventions: Drug: Atezolizumab
Drug: Tiragolumab

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

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 & 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): MEDSI Clinical Hospital on Pyatnitsky Highway
🇷🇺
Moscow, Moskovskaja Oblast, Russian Federation
Arizona Oncology Associates
🇺🇸
Phoenix, Arizona, United States
Kaiser Permanente - Irvine
🇺🇸
Irvine, California, United States
Augusta University
🇺🇸
Augusta, Georgia, United States
Oncology Associates of Oregon, P.C
🇺🇸
Eugene, Oregon, United States
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
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MEDSI Clinical Hospital on Pyatnitsky Highway
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation