This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Atezolizumab will be administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Hospital General Universitario de Elche
Elche, Alicante, Spain
Hospital Son Llatzer
Palma de Mallorca, Balearic Islands, Spain
Corporacio Sanitaria Parc Tauli
Sabadell, Barcelona, Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital Provincial de Castellon
Castellon, Castellon, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela, LA Coruna, Spain
Hospital de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, LAS Palmas, Spain
Hospital Universitario de Torrejon
Torrejón de Ardoz, Madrid, Spain
Clinica Universitaria de Navarra
Pamplona/iruña, Navarre, Spain
Hospital de Basurto
Bilbao, Vizcaya, Spain
...and 15 more locations
Number of Participants Who Discontinued Atezolizumab and/or Bevacizumab Due to Adverse Events (AE) of Grade ≥ 3
AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavourable 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. The severity of AEs was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) with the following grades: Grade 1 = asymptomatic or mild symptoms; Grade 2 = minimal, local, or non-invasive intervention indicated; Grade 3 = severe or medically significant, but not immediately life-threatening; Grade 4 = life-threatening consequences or urgent intervention indicated and Grade 5 = death related to AE.
Time frame: From Cycle 1 Day 1 up to 30 days after the final dose of the study drug or until initiation of another anti-cancer therapy, whichever occurred first (up to approximately 32 months)
Overall Survival (OS)
OS was defined as the time from initiation of study treatment to death from any cause. OS was analyzed using Kaplan-Meier (K-M) methods and Greenwood's formula. Any participant who did not die during the study was censored at the last known date to be alive.
Time frame: Up to 35 months
Progression-free Survival (PFS)
PFS was defined as the time from initiation of study treatment to the first occurrence of disease progression (PD) or death from any cause (whichever occurs first), as determined by the investigator according to Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (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 millimeters (mm). PFS was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study and were censored at the last known date to be alive or without disease progression.
Time frame: Up to 35 months
Objective Response Rate (ORR)
ORR = percentage of participants with a complete or partial response (CR or PR), on 2 consecutive investigator assessments ≥ 4 weeks apart in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1. CR = disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR = at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants without a post-baseline tumor assessment were considered non-responders. 95% confidence interval (CI) was derived using Wilson score intervals. Percentages have been rounded off.
Time frame: Up to 35 months
Time to Progression (TTP)
TTP was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). In addition to the relative increase of 20%, SOD must also demonstrate an absolute increase of ≥ 5 mm. TTP was analyzed using K-M methods and Greenwood's formula. Any participant who had no disease progression was censored at the last known date without disease progression.
Time frame: Up to 35 months
Duration of Response (DOR)
DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the 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. DOR was analyzed using K-M methods and Greenwood's formula. Any participant who did not experience disease progression or death during the study was censored at the last known date to be alive or without disease progression.
Time frame: Up to 35 months
Percentage of Participants Who Started Second-line Treatment
Participants who started second-line of treatment were assessed. Percentages have been rounded off.
Time frame: Up to 35 months
Change From Baseline in International Normalized Ratio (INR)
The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants to evaluate coagulation parameters.
Time frame: Baseline up to Cycle 42 (1 cycle = 21 days)
Change From Baseline in Albumin-Bilirubin (ALBI) Score
Blood samples were collected from participants to evaluate of ALBI grades. ALBI assessment grades of 1 to 3 was based on ALBI score calculation. ALBI score= log10 bilirubin (micromole per liter) \[μmol/L\] × 0.66 + albumin (grams per liter) \[g/L\] × -0.0852. ALBI score ≤ -2.60 = ALBI grade 1; -2.60 \< ALBI score ≤ -1.39 = ALBI grade 2 and -1.39 \< ALBI score = ALBI grade 3.
Time frame: Baseline up to Cycle 42 (1 cycle = 21 days)
Percentage of Participants With Ascites and/or Hepatic Encephalopathy
Deterioration of hepatic function was monitored by presence of ascites and/or hepatic encephalopathy.
Time frame: Up to approximately 32 months
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