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

Hoffmann-La Roche172 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

172

Conditions

Cervical Cancer

Interventions

TiragolumabDRUG

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.

AtezolizumabDRUG

Atezolizumab at a fixed dose of 1200 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (58)

Outcomes

Primary Outcomes

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.

Time frame: From randomization up to approximately 17 months

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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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, Estado de Bahia, Brazil

Hospital Araujo Jorge

Goiânia, Goiás, Brazil

Hospital de Caridade de Ijui

Ijuí, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, Brazil

...and 48 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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)..

Time frame: At Month 6

Pre-crossover Period: Overall Survival (OS)

OS was defined as the time of randomization to death from any cause.

Time frame: 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.

Time frame: At Months 6 and 12

Pre-crossover Period: Minimum Serum Concentration (Cmin) of Tiragolumab

Time frame: 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

Time frame: At 30 minutes post-dose on Cycle 1 Day 1 (1 Cycle = 21 days)

Pre-crossover Period: Cmin of Atezolizumab

Time frame: Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days)

Pre-crossover Period: Cmax of Atezolizumab

Time frame: 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).

Time frame: 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.

Time frame: Up to approximately 17 months