Colorectal Cancer
Conditions
Keywords
Locally advanced or Metastatic colorectal adenocarcinoma
Brief summary
This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.
Interventions
Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
DRUGCobimetinib
Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
DRUGRegorafenib
Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Disease-specific inclusion criteria: * Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer \[AJCC\] 7th edition) * Experienced disease progression or was intolerant to at least two systemic chemotherapy regimens for metastatic colorectal cancer that must have included fluroropyrimidines, irinotecan, and oxaliplatin; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion; disease progression must have occurred within 3 months of the last systemic therapy administration General inclusion criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Anticipated life expectancy greater than or equal to (\>=) 3 months * Adequate hematologic and end organ function * Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of less than \[\<\] 1 percent \[%\] per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib * Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier contraception during the treatment period and for 3 months after the last dose of either cobimetinib or regorafenib * Provide an archival or newly obtained tumor tissue sample
Exclusion criteria
* After the approximate 5% cap for microsatellite (MSI)-high participants is reached, only MSI-stable participants will be eligible * Once the 50% cap for wild-type RAS has been reached, only extended RAS-mutant participants will be eligible * Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment * Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1 * Uncontrolled tumor-related pain. Participants requiring narcotic pain medication must be on a stable regimen at study entry * Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed * Active or untreated central nervous system (CNS) metastases are excluded * Prior therapy with any cancer immunotherapy, MEK inhibitor, or regorafenib * Participants with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible * Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher * Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%, whichever is lower * Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 millimeters of Mercury (mmHg) despite optimal medical management * Human immunodeficiency virus (HIV) infection * Active tuberculosis infection * Severe infections within 2 weeks prior to Cycle 1 Day 1 * Active or chronic viral hepatitis B or C infection * History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration * Participants will be excluded if they currently have any of the risk factors as defined in the study protocol for retinal vein occlusion * History of autoimmune disease * History of idiopathic pulmonary fibrosis, organizing pneumonia, bronchiolitis obliterans, drug-induced pneumonitis, or idiopathic pneumonitis * History of organ transplantation including allogeneic bone marrow transplantation * Inability to swallow medications * Malabsorption condition that would alter the absorption of orally administered medications * Pregnant, lactating, breastfeeding, or intending to become pregnant during the study * Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization up to death due to any cause (up to approximately 20 months) | Overall survival is defined as the time (in months) between the date of randomization and the date of death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of Cobimetinib | Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) (up to approximately 2.5 years). | — |
| Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | From randomization up to disease progression or death due to any cause (up to approximately 20 months) | PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley. |
| Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1 | From randomization up to death due to any cause (up to approximately 20 months) | PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Objective response and its 95% CI were calculated using the Clopper-Pearson method. |
| Duration of Response (DOR) According to RECIST Version 1.1 | From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months) | DOR is defined as the period measured from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. Median DOR was estimated using the Kaplan-Meier method, and the 95% CI was calculated using the method of Brookmeyer and Crowley. |
| Percentage of Participants With Adverse Events (AEs) | Baseline, end of the study (up to approximately 2.5 years) | — |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Baseline, end of the study (up to approximately 2.5 years) | The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| Serum Concentration of Atezolizumab | Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 2.5 years. Detailed time frame is explained in the outcome measure description field. | Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infusion on Day 1 of Cycles 1 and 4; pre-infusion (0 hours) on Day 1 of Cycle 8 and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days) |
| Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4, 8, and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days) | — |
| Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Baseline, end of the study (up to approximately 2.5 years) | The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
Countries
Australia, Belgium, Canada, Hong Kong, Italy, Poland, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 490 participants were screened of whom only 363 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Regorafenib Participants received regorafenib 160 milligrams (mg) orally once daily on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first. | 90 |
| Cobimetinib + Atezolizumab Participants received cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first. | 183 |
| Atezolizumab Participants received atezolizumab monotherapy 1200 mg intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first. | 90 |
| Total | 363 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 62 | 136 | 72 |
| Overall Study | Lost to Follow-up | 0 | 3 | 2 |
| Overall Study | Sponsor decision | 18 | 29 | 11 |
| Overall Study | Withdrawal by Subject | 10 | 15 | 5 |
Baseline characteristics
| Characteristic | Regorafenib | Cobimetinib + Atezolizumab | Atezolizumab | Total |
|---|---|---|---|---|
| Age, Continuous | 58.4 Years STANDARD_DEVIATION 10.3 | 58.0 Years STANDARD_DEVIATION 11.9 | 56.7 Years STANDARD_DEVIATION 10.2 | 57.8 Years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 11 Participants | 5 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 77 Participants | 166 Participants | 82 Participants | 325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 3 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 18 Participants | 11 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 8 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) White | 71 Participants | 152 Participants | 73 Participants | 296 Participants |
| Sex: Female, Male Female | 39 Participants | 75 Participants | 31 Participants | 145 Participants |
| Sex: Female, Male Male | 51 Participants | 108 Participants | 59 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 62 / 90 | 136 / 183 | 72 / 90 |
| other Total, other adverse events | 78 / 80 | 173 / 179 | 81 / 90 |
| serious Total, serious adverse events | 19 / 90 | 71 / 183 | 15 / 90 |
Outcome results
Primary
Overall Survival (OS)
Overall survival is defined as the time (in months) between the date of randomization and the date of death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time frame: From randomization up to death due to any cause (up to approximately 20 months)
Population: Analysis was performed on the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib | Overall Survival (OS) | 8.51 months |
| Cobimetinib + Atezolizumab | Overall Survival (OS) | 8.87 months |
| Atezolizumab | Overall Survival (OS) | 7.10 months |
p-value: 0.987195% CI: [0.73, 1.38]Stratified Log-Rank
p-value: 0.33695% CI: [0.83, 1.71]Stratified Log-Rank
p-value: 0.968695% CI: [0.74, 1.38]Unstratified Log-Rank
p-value: 0.355395% CI: [0.83, 1.69]Unstratified Log-Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study
The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, end of the study (up to approximately 2.5 years)
Population: Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 4 | -6.44 units of a scale | Standard Deviation 18.84 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 48 | -2.78 units of a scale | Standard Deviation 4.81 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 44 | 0.00 units of a scale | Standard Deviation 13.61 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 28 | -8.33 units of a scale | Standard Deviation 17.25 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Treatment Discontinuation | -19.87 units of a scale | Standard Deviation 23.93 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 40 | 2.08 units of a scale | Standard Deviation 10.49 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 32 | -5.00 units of a scale | Standard Deviation 14.8 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 12 | -1.04 units of a scale | Standard Deviation 18.6 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 36 | 0.00 units of a scale | Standard Deviation 7.45 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 6 | -13.89 units of a scale | Standard Deviation 19.09 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 64 | -4.17 units of a scale | Standard Deviation 5.89 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 60 | -4.17 units of a scale | Standard Deviation 17.68 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 16 | -4.39 units of a scale | Standard Deviation 18.08 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 3 | -21.30 units of a scale | Standard Deviation 28.6 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 56 | -5.56 units of a scale | Standard Deviation 9.62 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 20 | 0.52 units of a scale | Standard Deviation 18.38 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 8 | -8.05 units of a scale | Standard Deviation 15.98 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 52 | 4.17 units of a scale | Standard Deviation 15.96 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 24 | -3.79 units of a scale | Standard Deviation 20.19 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 32 | 1.39 units of a scale | Standard Deviation 23.79 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 4 | -7.00 units of a scale | Standard Deviation 21.24 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 8 | -4.38 units of a scale | Standard Deviation 22.58 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 12 | -4.25 units of a scale | Standard Deviation 18.51 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 16 | -1.94 units of a scale | Standard Deviation 23.64 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 20 | 4.71 units of a scale | Standard Deviation 23.28 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 24 | 3.75 units of a scale | Standard Deviation 23.95 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 28 | 0.00 units of a scale | Standard Deviation 31.18 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 64 | 6.67 units of a scale | Standard Deviation 24.58 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 36 | 5.56 units of a scale | Standard Deviation 16.86 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 40 | 11.36 units of a scale | Standard Deviation 12.51 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 44 | 9.52 units of a scale | Standard Deviation 15.63 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 48 | 10.61 units of a scale | Standard Deviation 15.85 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 52 | 12.12 units of a scale | Standard Deviation 17.62 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 56 | 18.75 units of a scale | Standard Deviation 9.71 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 60 | 16.67 units of a scale | Standard Deviation 15.59 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 68 | 0.00 units of a scale | — |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Treatment Discontinuation | -14.27 units of a scale | Standard Deviation 25.98 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 3 | -6.11 units of a scale | Standard Deviation 22.15 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 6 | -15.83 units of a scale | Standard Deviation 15.44 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 30 | 0.00 units of a scale | — |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 33 | 0.00 units of a scale | — |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 36 | 0.00 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 21 | 6.25 units of a scale | Standard Deviation 19.29 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 3 | -11.36 units of a scale | Standard Deviation 20.16 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 54 | 12.50 units of a scale | Standard Deviation 5.89 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 18 | 7.41 units of a scale | Standard Deviation 18.37 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 3 | -1.70 units of a scale | Standard Deviation 17.76 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 57 | 8.33 units of a scale | Standard Deviation 0 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 15 | -4.69 units of a scale | Standard Deviation 12.16 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 36 | 8.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 60 | 8.33 units of a scale | Standard Deviation 0 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 12 | -3.67 units of a scale | Standard Deviation 15.42 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 6 | -11.67 units of a scale | Standard Deviation 15.14 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 9 | -4.84 units of a scale | Standard Deviation 15.78 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 33 | 6.25 units of a scale | Standard Deviation 17.18 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 33 | 8.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 36 | 16.67 units of a scale | Standard Deviation 25 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 39 | 22.22 units of a scale | Standard Deviation 17.35 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 30 | 5.00 units of a scale | Standard Deviation 15.14 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Treatment Discontinuation | -14.53 units of a scale | Standard Deviation 20.48 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 42 | 25.00 units of a scale | Standard Deviation 16.67 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 27 | -2.38 units of a scale | Standard Deviation 19.07 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 6 | -4.86 units of a scale | Standard Deviation 17.43 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 45 | 19.44 units of a scale | Standard Deviation 9.62 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 24 | -6.94 units of a scale | Standard Deviation 19.31 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Long Term Follow-up Month 30 | 8.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 48 | 8.33 units of a scale | Standard Deviation 0 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study | Week 51 | 8.33 units of a scale | Standard Deviation 0 |
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score
The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, end of the study (up to approximately 2.5 years)
Population: Analysis was performed on PRO-evaluable population. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 52 | -5.00 units of a scale | Standard Deviation 6.38 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 48 | -13.33 units of a scale | Standard Deviation 6.67 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 28 | -5.00 units of a scale | Standard Deviation 9.92 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 12 | -7.78 units of a scale | Standard Deviation 13.57 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 44 | 1.67 units of a scale | Standard Deviation 3.33 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 32 | -4.67 units of a scale | Standard Deviation 11.35 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 6 | -14.07 units of a scale | Standard Deviation 17.14 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 40 | -5.00 units of a scale | Standard Deviation 11.39 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 36 | -12.22 units of a scale | Standard Deviation 14.25 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Treatment Discontinuation | -17.00 units of a scale | Standard Deviation 19.21 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 64 | -6.67 units of a scale | Standard Deviation 18.86 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 16 | -9.12 units of a scale | Standard Deviation 17.1 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 8 | -8.97 units of a scale | Standard Deviation 13.95 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 60 | -3.33 units of a scale | Standard Deviation 4.71 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 20 | -7.92 units of a scale | Standard Deviation 19.51 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 4 | -6.52 units of a scale | Standard Deviation 13.9 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 56 | -2.22 units of a scale | Standard Deviation 3.85 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 24 | -5.45 units of a scale | Standard Deviation 9.81 |
| Regorafenib | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 3 | -22.29 units of a scale | Standard Deviation 24.29 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 64 | -2.67 units of a scale | Standard Deviation 10.11 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 4 | -3.92 units of a scale | Standard Deviation 11.05 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 8 | -3.23 units of a scale | Standard Deviation 16.15 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 12 | -5.10 units of a scale | Standard Deviation 15.54 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 16 | -5.11 units of a scale | Standard Deviation 16.67 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 20 | -0.87 units of a scale | Standard Deviation 14.95 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 24 | -3.00 units of a scale | Standard Deviation 18.67 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 28 | -3.16 units of a scale | Standard Deviation 15.29 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 32 | -10.74 units of a scale | Standard Deviation 21.1 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 36 | -1.78 units of a scale | Standard Deviation 16.23 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 40 | -0.61 units of a scale | Standard Deviation 16.18 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 44 | 3.33 units of a scale | Standard Deviation 16.07 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 48 | 1.82 units of a scale | Standard Deviation 9.47 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 52 | 3.64 units of a scale | Standard Deviation 10.05 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 56 | 5.00 units of a scale | Standard Deviation 13.69 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 60 | 2.96 units of a scale | Standard Deviation 11.6 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 68 | 0.00 units of a scale | Standard Deviation 0 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Treatment Discontinuation | -16.24 units of a scale | Standard Deviation 23.49 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 3 | -15.11 units of a scale | Standard Deviation 16.8 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 6 | -10.00 units of a scale | Standard Deviation 14.14 |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 30 | -20.00 units of a scale | — |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 33 | -20.00 units of a scale | — |
| Cobimetinib + Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 36 | -20.00 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 3 | -20.00 units of a scale | Standard Deviation 26.67 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 54 | 0.00 units of a scale | Standard Deviation 18.86 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 21 | -8.33 units of a scale | Standard Deviation 17.37 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 6 | -0.14 units of a scale | Standard Deviation 12.49 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 57 | 0.00 units of a scale | Standard Deviation 18.86 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 18 | -3.70 units of a scale | Standard Deviation 14.95 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 36 | 13.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 60 | 0.00 units of a scale | Standard Deviation 18.86 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 15 | -7.08 units of a scale | Standard Deviation 14.9 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 3 | -1.50 units of a scale | Standard Deviation 10.56 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 6 | -8.00 units of a scale | Standard Deviation 15.92 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 12 | -6.40 units of a scale | Standard Deviation 16.61 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 33 | 13.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 36 | 4.44 units of a scale | Standard Deviation 15.4 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 39 | 2.22 units of a scale | Standard Deviation 19.25 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 33 | -1.67 units of a scale | Standard Deviation 13.74 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Treatment Discontinuation | -11.79 units of a scale | Standard Deviation 19.01 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 42 | 4.44 units of a scale | Standard Deviation 15.4 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 30 | -8.00 units of a scale | Standard Deviation 20.76 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 9 | -6.67 units of a scale | Standard Deviation 17.19 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 45 | 4.44 units of a scale | Standard Deviation 15.4 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 27 | 0.95 units of a scale | Standard Deviation 15.6 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Long Term Follow Up Month 30 | 13.33 units of a scale | — |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 48 | 0.00 units of a scale | Standard Deviation 18.86 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 51 | 0.00 units of a scale | Standard Deviation 18.86 |
| Atezolizumab | Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score | Week 24 | 0.00 units of a scale | Standard Deviation 16.87 |
Secondary
Duration of Response (DOR) According to RECIST Version 1.1
DOR is defined as the period measured from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. Median DOR was estimated using the Kaplan-Meier method, and the 95% CI was calculated using the method of Brookmeyer and Crowley.
Time frame: From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months)
Population: DOR was assessed in participants who had an objective response during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib | Duration of Response (DOR) According to RECIST Version 1.1 | 4.50 months |
| Cobimetinib + Atezolizumab | Duration of Response (DOR) According to RECIST Version 1.1 | 1.97 months |
| Atezolizumab | Duration of Response (DOR) According to RECIST Version 1.1 | 2.81 months |
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: Baseline, end of the study (up to approximately 2.5 years)
Population: Analysis was performed on the SAF population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regorafenib | Percentage of Participants With Adverse Events (AEs) | Serious AEs | 23.8 percentage of participants |
| Regorafenib | Percentage of Participants With Adverse Events (AEs) | Non-serious AEs | 97.5 percentage of participants |
| Cobimetinib + Atezolizumab | Percentage of Participants With Adverse Events (AEs) | Serious AEs | 39.7 percentage of participants |
| Cobimetinib + Atezolizumab | Percentage of Participants With Adverse Events (AEs) | Non-serious AEs | 97.8 percentage of participants |
| Atezolizumab | Percentage of Participants With Adverse Events (AEs) | Serious AEs | 16.7 percentage of participants |
| Atezolizumab | Percentage of Participants With Adverse Events (AEs) | Non-serious AEs | 93.3 percentage of participants |
Secondary
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Time frame: Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4, 8, and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)
Population: Analysis was performed on the SAF population and included participants with at least one predose and one postdose ATA assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | 43.8 percentage of participants |
| Cobimetinib + Atezolizumab | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab | 41.3 percentage of participants |
Secondary
Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1
PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions). Objective response and its 95% CI were calculated using the Clopper-Pearson method.
Time frame: From randomization up to death due to any cause (up to approximately 20 months)
Population: Analysis was performed on evaluable participants in the ITT population with measurable disease at baseline, as determined by the investigator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib | Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1 | 2.2 percentage of participants |
| Cobimetinib + Atezolizumab | Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1 | 2.7 percentage of participants |
| Atezolizumab | Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1 | 2.2 percentage of participants |
p-value: 195% CI: [-3.92, 4.94]Stratified Cochrane-Mantel-Haenszel
p-value: 195% CI: [-4.89, 4.89]Stratified Cochran-Mantel-Haenszel
Secondary
Plasma Concentration of Cobimetinib
Time frame: Predose (0 hours) and 3 to 6 hours after dose on Day 15 of Cycles 1 and 4 (1 cycle = 28 days) (up to approximately 2.5 years).
Population: The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Only included participants in the Cobimetnib arm
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib | Plasma Concentration of Cobimetinib | Cycle 1 Day 15 - Predose | 195 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 190 |
| Regorafenib | Plasma Concentration of Cobimetinib | Cycle 1 Day 15 - Postdose | 362 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 89.4 |
| Regorafenib | Plasma Concentration of Cobimetinib | Cycle 4 Day 15 - Predose | 94.3 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 741.9 |
| Regorafenib | Plasma Concentration of Cobimetinib | Cycle 4 Day 15 - Postdose | 210 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 273.4 |
Secondary
Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
PFS was defined as the time from randomization to disease progression as determined by the investigator with the use of RECIST v1.1 or death due to any cause, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). For non-target lesions, disease progression was defined as unequivocal progression of existing lesions. The appearance of one or more new lesions was also considered progression. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
Time frame: From randomization up to disease progression or death due to any cause (up to approximately 20 months)
Population: Analysis was performed on the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib | Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 2.00 months |
| Cobimetinib + Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 1.91 months |
| Atezolizumab | Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 1.94 months |
p-value: 0.120895% CI: [0.94, 1.65]Stratified Log-Rank
p-value: 0.050995% CI: [1, 1.94]Stratified Log-Rank
p-value: 0.172695% CI: [0.92, 1.6]Unstratified Log-Rank
p-value: 0.046795% CI: [1, 1.91]Unstratified Log-Rank
Secondary
Serum Concentration of Atezolizumab
Pre-infusion (0 hours) on Day 1 of Cycles 1 to 4; 30 minutes post-infusion on Day 1 of Cycles 1 and 4; pre-infusion (0 hours) on Day 1 of Cycle 8 and every 8 cycles thereafter; at treatment discontinuation; 120 days after treatment discontinuation (up to approximately 2.5 years) (1 cycle = 28 days)
Time frame: Pre-infusion (0 hours) on Day 1 of Cycle 1 up to approximately 2.5 years. Detailed time frame is explained in the outcome measure description field.
Population: The pharmacokinetic (PK) evaluable population included all participants who received any dose of study medication and who had at least one post-baseline PK sample available. Also, only included participants to whom Atezolizumab was administered.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 1 Day 1 - Predose | NA microgram/milliliter (ug/mL) | — |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 4 Day 1 - 30 min post dose | 487 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 41.5 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 81.5 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 35.7 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 5 Day 1 - Predose | 155 microgram/milliliter (ug/mL) | — |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 5 Day 1 - 30 min post dose | 456 microgram/milliliter (ug/mL) | — |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 8 Day 1 - Predose | 138 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 54.6 |
| Regorafenib | Serum Concentration of Atezolizumab | Treatment Discontinuation | 97.9 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 114.5 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 16 Day 1 - Predose | 226 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 24.4 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 2 Day 1 - 30 min post dose | 56.2 microgram/milliliter (ug/mL) | — |
| Regorafenib | Serum Concentration of Atezolizumab | Unscheduled | 0.784 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 2159.5 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 3 Day 1 - Predose | 118 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 45.4 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 1 Day 1 - 30 min post dose | 348 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 150 |
| Regorafenib | Serum Concentration of Atezolizumab | Cycle 4 Day 1 - Predose | 146 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 52.4 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Unscheduled | 0.539 microgram/milliliter (ug/mL) | — |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Treatment Discontinuation | 76.6 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 184.9 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 1 Day 1 - Predose | NA microgram/milliliter (ug/mL) | — |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 1 Day 1 - 30 min post dose | 259 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 141 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 2 Day 1 - Predose | 68.2 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 191.2 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 3 Day 1 - Predose | 133 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 51.2 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 4 Day 1 - Predose | 167 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 48.4 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 4 Day 1 - 30 min post dose | 415 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 37.2 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 8 Day 1 - Predose | 198 microgram/milliliter (ug/mL) | Geometric Coefficient of Variation 52.6 |
| Cobimetinib + Atezolizumab | Serum Concentration of Atezolizumab | Cycle 16 Day 1 - Predose | 264 microgram/milliliter (ug/mL) | — |