Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Dose Limiting Toxicities (DLTs) |
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any >= Grade 2 pneumonitis that does not resolve to <= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to <= Grade 1 or baseline within 14 days, liver transaminase elevation > 8 × upper limit of normal (ULN) or total bilirubin > 5 × ULN, aspartate aminotransferase or alanine aminotransferase > 3 × ULN with concurrent increase in total bilirubin > 2 × ULN without evidence of cholestasis or alternative explanations, and any >= Grade 3 non-irAE (except for the protocol stated conditions). |
From Day 1 to Day 28 after first dose of study drug |
|
| Primary |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Primary |
Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters |
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Primary |
Number of Participants With Abnormal Vital Signs Reported as TEAEs |
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Primary |
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events |
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) |
Disease assessments based on investigator assessments and BICR review were determined by using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) guidelines. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Disease Control Rate (DCR) Based on Investigator Assessments and BICR |
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The DCR is defined as a BOR of confirmed CR, confirmed PR, or stable disease (SD). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Time to Response (TTR) Based on Investigator Assessments and BICR |
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTR is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Duration of Response (DoR) Based on Investigator Assessments and BICR |
The DoR is defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments and BICR review by using RECIST v1.1 or death in absence of disease progression. A confirmed CR is defined in above outcome measures. The PD is defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. The DoR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Time to Progression (TTP) Based on Investigator Assessments and BICR |
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTP was defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 to the first documentation of radiographic disease progression. However, if the participant died without tumor progression, they were censored at the time of death. Participants with no documented PD by the data cutoff date for TTP analysis were censored at the date of their last evaluable disease assessment. The TTP was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Progression Free Survival (PFS) Based on Investigator Assessments and BICR |
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The PFS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of radiographic disease progression or death due to any cause, whichever occurs first. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared with the nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. Participants who were alive with no documented PD by the data cutoff date for PFS analysis were censored at the date of their last evaluable disease assessment. The PFS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
|
| Secondary |
Overall Survival (OS) |
The OS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until death due to any cause. If there was no death reported for a participant by the data cut-off date for overall survival analysis, OS was censored at the last known alive date. The OS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) |
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