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
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 172
- Locations
- 58
- Primary Endpoint
- Pre-crossover Period: Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR)
Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Tiragolumab plus Atezolizumab
Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Tiragolumab (Drug)
Tiragolumab plus Atezolizumab
Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Atezolizumab (Drug)
Atezolizumab
Participants will receive atezolizumab monotherapy until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Atezolizumab (Drug)
Outcomes
Primary Outcomes
Pre-crossover Period: Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR)
Time Frame: From randomization up to approximately 17 months
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.
Secondary Outcomes
- Pre- and Post-crossover Periods: Number of Participants With Adverse Events (AEs)(Up to approximately 50.3 months)
- 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: IRC-assessed Duration of Response (DOR)(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)(From randomization up to approximately 17 months)
- Pre-crossover Period: Investigator-assessed Best Clinical Response (BCR) Rate(From randomization up to approximately 17 months)
- Pre-crossover Period: Investigator-assessed Duration of BCR(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: Cmin of Atezolizumab(Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (1 cycle = 21 days))
- Pre-crossover Period: IRC-assessed Progression-free Survival (PFS)(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(At Month 6)
- Pre-crossover Period: Overall Survival (OS)(From randomization to death from any cause (up to approximately 17 months))
- Pre-crossover Period: OS Rate at 6 Months and 12 Months(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: 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(Up to approximately 17 months)
- Pre-crossover Period: Percentage of Participants With ADAs to Atezolizumab(Up to approximately 17 months)