Carcinoma, Hepatocellular
Conditions
Brief summary
This is a Phase IIIb, one arm, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab + bevacizumab in patients with unresectable HCC who have received no prior systemic treatment.
Interventions
DRUGAtezolizumab
Atezolizumab 1200 mg IV infusion q3w
DRUGBevacizumab
Bevacizumab 15 mg/kg IV Q3W
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable HCC with diagnosis confirmed by histology, with a biopsy within 6 months from recruitment; * Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies; * No prior systemic therapy for HCC; * At least one measurable untreated lesion; * Patients who received prior local therapy are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1; * ECOG Performance Status of 0 or 1 within 7 days prior to recruitment; * Child-Pugh class A within 7 days prior to recruitment; * Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed. In case of varices at high risk of bleeding (corresponding to medium (F2) or large (F3) varices, or F1 varices with cherry red spots or red wale marking) prophylatic treatment per local standard of care must be adopted prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure provided they had no varices at high risk of bleeding; * Adequate hematologic and end-organ function * Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade \<= 1 prior to study entry, with the exception of alopecia * Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200µL, and have an undetectable viral load; * In patients with viral HCC, documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test; * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs. * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
Exclusion criteria
* History of leptomeningeal disease or brain metastases; * Active or history of autoimmune disease or immune deficiency; * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; * Known active tuberculosis; * Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina; * History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death; * Prior allogeneic stem cell or solid organ transplantation; * Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab; * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC; * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding; * A prior bleeding event due to oesophageal and/or gastric varices within 6 months prior to initiation of study treatment; * Clinically evident ascites; * Co-infection of HBV and HCV; * Co-infection with HBV and hepatitis D viral infection; * Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases; * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; * Clinically significant uncontrolled or symptomatic hypercalcemia; * Inadequately controlled arterial hypertension; * Significant vascular disease within 6 months prior to initiation of study treatment; * History of haemoptysis; * Evidence of bleeding diathesis or significant coagulopathy; * History of gastrointestinal (GI) fistula, GI perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment; * History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to initiation of study treatment; * Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses of large volume; * Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage | Up to approximately 47.6 months | An adverse event (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. Severity of AEs was graded using NCI CTCAE v5.0. Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=Death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 47.6 months | OS was defined as the time from initiation of study treatment to death from any cause. Kaplan-Meier (K-M) method was used to estimate the OS. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to approximately 47.6 months | 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. TEAEs are defined as AEs with onset date on or after the start of the first study treatment component. Number of participants with any TEAEs are reported here. |
| Progression-free Survival (PFS) | Up to approximately 47.6 months | 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 Tumors, 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). Participants alive and without any PD were censored at the last assessment date. K-M method was used to estimate the PFS. |
| Objective Response Rate (ORR) | Up to approximately 47.6 months | ORR was defined as the percentage of participants with complete or partial response (CR or PR), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have 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. |
| Duration of Response (DOR) | Up to approximately 47.6 months | 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 or any pathological lymph nodes must have 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. Participants who were alive and without any PD were censored at the last assessment date. K-M method was used to estimate the DOR. |
| Post-progression Survival (PPS) | Up to approximately 47.6 months | PPS was defined as the time from the first occurrence of PD as determined by the investigator according to RECIST v1.1 to death from any cause. 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. Participants who were alive were censored at the last assessment date. K-M method was used to estimate the PPS. |
| Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days) | Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, &/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A subset of 14 symptoms most applicable to current treatments were selected for this study. Symptoms were selected based on toxicities associated with the drug's class, mechanism of action, or mode of administration, and toxicities reported with the drug in another indication. Number of participants who reported severe symptoms per the PRO-CTCAE questionnaire on Day 1 of each cycle is reported here. |
| Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days) | Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, &/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A subset of 14 symptoms most applicable to current treatments were selected for this study. Symptoms were selected based on toxicities associated with the drug's class, mechanism of action, or mode of administration, &toxicities reported with the drug in another indication. Number of participants who reported very severe symptoms per the PRO-CTCAE questionnaire on Day 1 of each cycle is reported here. |
| Time to Progression (TTP) | Up to approximately 47.6 months | 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%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Participants without any PD were censored at the last assessment date. K-M method was used to estimate the TTP. |
Other
| Measure | Time frame |
|---|---|
| Number of Participants Starting Second or Further Lines of Treatment | Up to approximately 47.6 months |
Countries
Italy
Participant flow
Recruitment details
A total of 152 participants with unresectable hepatocellular carcinoma (HCC) and no prior systemic treatment took part in the study at 21 investigative sites in Italy from 25 August 2020 to 13 August 2024.
Pre-assignment details
Participants received atezolizumab in combination with bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Of the 152 participants enrolled, three participants did not receive any treatment.
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab + Bevacizumab Participants received atezolizumab, 1200 mg as IV infusion, along with bevacizumab, 15 mg/kg, also as IV infusion, Q3W on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator. | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death Due To Progressive Disease | 40 |
| Overall Study | Death Other Than Progressive Disease | 60 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Participant Discontinued From Study as per Protocol | 6 |
| Overall Study | Progressive Disease | 1 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | Atezolizumab + Bevacizumab |
|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 10.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 141 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 145 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 102 / 149 |
| other Total, other adverse events | 142 / 149 |
| serious Total, serious adverse events | 62 / 149 |
Outcome results
Primary
Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage
An adverse event (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. Severity of AEs was graded using NCI CTCAE v5.0. Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=Death related to AE.
Time frame: Up to approximately 47.6 months
Population: Safety analysis population included all enrolled participants who had at least one full or partial administration of atezolizumab plus bevacizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab + Bevacizumab | Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage | Grade 3 | 17 Participants |
| Atezolizumab + Bevacizumab | Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage | Grade 4 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants With Grade 3-5 National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE V5) Bleeding/Haemorrhage | Grade 5 | 2 Participants |
Secondary
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 or any pathological lymph nodes must have 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. Participants who were alive and without any PD were censored at the last assessment date. K-M method was used to estimate the DOR.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study. Overall number analyzed is the number of participants with an objective response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Bevacizumab | Duration of Response (DOR) | 17.35 months |
Secondary
Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire
Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, &/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A subset of 14 symptoms most applicable to current treatments were selected for this study. Symptoms were selected based on toxicities associated with the drug's class, mechanism of action, or mode of administration, and toxicities reported with the drug in another indication. Number of participants who reported severe symptoms per the PRO-CTCAE questionnaire on Day 1 of each cycle is reported here.
Time frame: From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days)
Population: Safety analysis population included all enrolled participants who had at least one full or partial administration of atezolizumab plus bevacizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 1 Day 1 | 39 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 2 Day 1 | 33 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 3 Day 1 | 23 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 4 Day 1 | 30 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 5 Day 1 | 23 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 6 Day 1 | 22 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 7 Day 1 | 17 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 8 Day 1 | 14 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 9 Day 1 | 19 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 10 Day 1 | 16 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 11 Day 1 | 17 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 12 Day 1 | 16 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 13 Day 1 | 13 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 14 Day 1 | 13 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 15 Day 1 | 9 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 16 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 17 Day 1 | 10 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 18 Day 1 | 10 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 19 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 20 Day 1 | 11 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 21 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 22 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 23 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 24 Day 1 | 10 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 25 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 26 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 27 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 28 Day 1 | 10 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 29 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 30 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 31 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 32 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 33 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 34 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 35 Day 1 | 9 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 36 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 37 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 38 Day 1 | 9 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 39 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 40 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 41 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 42 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 43 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 44 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 45 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 46 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 47 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 48 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 49 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 50 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 51 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 52 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 53 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 54 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 55 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 56 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 57 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 58 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 59 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 60 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 61 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 62 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Severe Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire | Cycle 63 Day 1 | 0 Participants |
Secondary
Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire
Participants self-reported symptomatic AEs using PRO-CTCAE, a validated item bank used to characterize presence, frequency of occurrence, severity, &/or degree of interference with daily function of 78 patient-reportable symptomatic treatment toxicities. PRO-CTCAE contains questions that are rated either dichotomously (for determination of presence vs. absence) or on a 5-point Likert scale (for determination of frequency of occurrence,severity,& interference with daily function). Treatment toxicities can occur with observable signs (e.g.,vomiting)/ non-observable symptoms (e.g.,nausea). A subset of 14 symptoms most applicable to current treatments were selected for this study. Symptoms were selected based on toxicities associated with the drug's class, mechanism of action, or mode of administration, &toxicities reported with the drug in another indication. Number of participants who reported very severe symptoms per the PRO-CTCAE questionnaire on Day 1 of each cycle is reported here.
Time frame: From Cycle 1 Day 1 to Cycle 63 Day 1 (1 Cycle = 21 days)
Population: Safety analysis population included all enrolled participants who had at least one full or partial administration of atezolizumab plus bevacizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 1 Day 1 | 15 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 2 Day 1 | 18 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 3 Day 1 | 12 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 4 Day 1 | 12 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 5 Day 1 | 10 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 6 Day 1 | 11 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 7 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 8 Day 1 | 11 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 9 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 10 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 11 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 12 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 13 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 14 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 15 Day 1 | 7 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 16 Day 1 | 8 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 17 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 18 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 19 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 20 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 21 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 22 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 23 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 24 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 25 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 26 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 27 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 28 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 29 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 30 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 31 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 32 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 33 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 34 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 35 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 36 Day 1 | 3 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 37 Day 1 | 6 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 38 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 39 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 40 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 41 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 42 Day 1 | 5 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 43 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 44 Day 1 | 4 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 45 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 46 Day 1 | 2 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 47 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 48 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 49 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 50 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 51 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 52 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 53 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 54 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 55 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 56 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 57 Day 1 | 1 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 58 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 59 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 60 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 61 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 62 Day 1 | 0 Participants |
| Atezolizumab + Bevacizumab | Number of Participants Reporting Very Severe Symptoms in PRO-CTCAE Questionnaire | Cycle 63 Day 1 | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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. TEAEs are defined as AEs with onset date on or after the start of the first study treatment component. Number of participants with any TEAEs are reported here.
Time frame: Up to approximately 47.6 months
Population: Safety analysis population included all enrolled participants who had at least one full or partial administration of atezolizumab plus bevacizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Atezolizumab + Bevacizumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 144 Participants |
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with complete or partial response (CR or PR), as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have 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.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab + Bevacizumab | Objective Response Rate (ORR) | 28.29 percentage of participants |
Secondary
Overall Survival (OS)
OS was defined as the time from initiation of study treatment to death from any cause. Kaplan-Meier (K-M) method was used to estimate the OS.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Bevacizumab | Overall Survival (OS) | 20.76 months |
Secondary
Post-progression Survival (PPS)
PPS was defined as the time from the first occurrence of PD as determined by the investigator according to RECIST v1.1 to death from any cause. 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. Participants who were alive were censored at the last assessment date. K-M method was used to estimate the PPS.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study. Overall number analyzed is the number of participants with a progressive disease.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Bevacizumab | Post-progression Survival (PPS) | 11.27 months |
Secondary
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 Tumors, 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). Participants alive and without any PD were censored at the last assessment date. K-M method was used to estimate the PFS.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Bevacizumab | Progression-free Survival (PFS) | 8.80 months |
Secondary
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%, the SOD must also demonstrate an absolute increase of ≥ 5 mm. Participants without any PD were censored at the last assessment date. K-M method was used to estimate the TTP.
Time frame: Up to approximately 47.6 months
Population: ITT population included all participants who signed the ICF and were enrolled in the study. Overall number analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Bevacizumab | Time to Progression (TTP) | 11.24 months |
Other Pre-specified
Number of Participants Starting Second or Further Lines of Treatment
Time frame: Up to approximately 47.6 months
Population: Per protocol, this is an exploratory outcome measure; therefore, the results have not been reported.