Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Dose-limiting Toxicities in the Dose-escalation Phase |
A DLT was defined as any Grade 3 or higher treatment-related toxicity that occurred during the DLT-evaluation period including any >= Grade 3 colitis or >= Grade 3 immune-related adverse event (irAE; AEs of immune nature in the absence of a clear alternative etiology) including rash, pruritus, or diarrhea that did not downgrade to =< Grade 2 within 3 days after onset of the event despite maximal supportive care including systemic corticosteroids. The DLT-evaluation period for 0.1 to 10 mg/kg arms was from Day 1 to Day 28 of first dose and for 15 mg/kg arm was from Day 1 to Day 42 of first dose. |
For MEDI4736 0.1 to MEDI4736 10 mg/kg arms: from Day 1 to Day 28 of first dose; for MEDI4736 15 mg/kg arm: from Day 1 to Day 42 of first dose |
|
| Primary |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
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. |
From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years) |
|
| Primary |
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of coagulation, urine, hematology, and serum chemistry. |
From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years) |
|
| Primary |
Number of Participants With Abnormal Vital Signs Reported as TEAEs in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body weight, body temperature, blood pressure, pulse rate, and respiratory rate). |
From Day 1 through 90 days after the last dose of study drug (approximately 5.25 years) |
|
| Primary |
Number of Participants With Change From Baseline in QT/QTc Interval in Local Electrocardiogram in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
Number of participants with change from baseline in notable QT/QTc interval in local electrocardiogram (ECG) are reported. The data for >0 participants with notable QT/QTc interval in local ECG from baseline are reported. |
From Baseline (Day 1) through 90 days after the last dose of study drug (approximately 5.25 years) |
|
| Primary |
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) in Participants With Non-squamous NSCLC Who Had Received 2 or More Prior Lines of Therapy in the Dose-expansion Phase |
The ORR assessed by BICR in participants with non-squamous NSCLC who had received 2 or more prior lines of therapy is reported. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Primary |
ORR Assessed by BICR in Participants With Squamous NSCLC Who Had Received 1 and 2 or More Prior Lines of Therapy in the Dose-expansion Phase |
The ORR assessed by BICR in participants with squamous NSCLC who had received 1 and 2 or more prior lines of therapy is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Primary |
ORR Assessed by BICR in Participants With UC Post-platinum (Programmed Cell Death Ligand [PD-L1] Status High) Who Had Received at Least 1 Line of Prior Therapy (2L+) in the Dose-expansion Phase |
The ORR assessed by BICR in participants with UC post-platinum PD-L1 status high 2L+ is reported. The ORR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Area Under the Serum Concentration-time Curve up to the Last Measurable Concentration (AUClast) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase |
Area under the concentration-time curve from time zero to the last measurable concentration (AUClast) of MEDI4736 is reported. |
After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg) |
|
| Secondary |
Maximum Serum Concentration (Cmax) of MEDI4736 After the First Dose in the Dose-escalation and Dose-exploration Phase |
The Cmax of MEDI4736 is reported. |
After the first dose between Day 0 and Day 15 (Day 1 [pre and post dose] and predose of Dose 2 for all cohorts; Days 3, 5, 10 for Cohorts 0.1mg/kg to 10 mg/kg; Days 3, 5, 10, 15 for Cohort 15 mg/kg; Day 15 for Cohort 20 mg/kg) |
|
| Secondary |
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI4736 in the Dose-escalation, Dose-exploration Phase, and Dose-expansion Phase. |
Number of participants with positive ADA titer to MEDI4736 are reported. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to a 4-fold or higher level following drug administration; persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment; and transient positive is defined as having at least one post-baseline ADA-positive assessment and not fulfilling the condition of persistent positive. |
Escalation: Day1 of Dose(D)1 & D3, even numbered doses after D4; Exploration: Day1 of D1 & D2, even numbered doses after D2; Expansion: Day1 of D1, every 12 weeks since D3; all phases: till EOT, 30 days and 3 and 6 months post last dose (~5.25 years) |
|
| Secondary |
Number of Participants With Best Overall Response (BOR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
The BOR assessed by BICR based on RECIST v1.1 in NSCLC and SCCHN cohorts is reported. The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE). 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 nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Number of Participants With BOR Assessed by Investigator in the Dose-escalation, Dose-exploration, and Dose-expansion Phase |
The BOR assessed by investigator based on RECIST v1.1 is reported. The BOR includes CR, PR, SD, PD, and NE. 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 nontarget lesion. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Duration of Response (DoR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
The DoR assessed by BICR in NSCLC and SCCHN cohorts is reported. The DoR is defined as the duration from the first documentation of objective response (OR) (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. 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 28 days 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) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DoR Assessed by Investigator in the Dose-expansion Phase |
The DoR in participants assessed by the investigator is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. 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 28 days 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) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Disease Control Rate (DCR) Assessed by BICR in NSCLC and SCCHN Cohort in the Dose-expansion Phase |
Percentage of participants with disease control assessed by BICR in NSCLC and SCCHN cohorts is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. 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 28 days 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) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days 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. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DCR Assessed by Investigator in the Dose-expansion Phase |
Percentage of participants with disease control assessed by the investigator is reported. Disease control is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. 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 28 days 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) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days 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. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Progression-free Survival (PFS) Assessed by BICR in NSCLC Cohort in the Dose-expansion Phase |
The PFS assessed by BICR in NSCLC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
PFS Assessed by BICR in SCCHN Cohort in the Dose-expansion Phase |
The PFS assessed by BICR in SCCHN cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
PFS Assessed by Investigator in the Dose-expansion Phase |
The PFS assessed by the investigator is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
OS in the Dose-Expansion Phase |
OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
ORR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The ORR assessed by BICR in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
ORR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The ORR assessed by the investigator in UC cohort is reported. The ORR is defined as confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. A confirmed CR is defined as two CRs that were separated by at least 28 days with no evidence of progression in-between. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. A confirmed PR is defined as two PRs or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DoR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The DoR assessed by BICR in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. 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 28 days 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) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DoR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The DoR assessed by investigator in UC cohort is reported. The DoR is defined as the duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. 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 28 days 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) or an un-confirmed PR and an un-confirmed CR that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DCR Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
Percentage of participants with disease control assessed by BICR in UC cohort is reported. The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. 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 28 days 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) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days 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. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
DCR Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
Percentage of participants with disease control assessed by investigator in UC cohort is reported. Disease control is defined as a best overall response of confirmed CR, confirmed PR, or SD based on RECIST v1.1. 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 28 days 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) or an un-confirmed PR and an unconfirmed CR that were separated by at least 28 days with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for disease progression. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
PFS Assessed by BICR in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The PFS assessed by BICR in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
PFS Assessed by Investigator in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The PFS assessed by the investigator in UC cohort is reported. The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
OS in UC Cohort (PD-L1 Low/Negative, Total, and PD-L1 High) in the Dose-expansion Phase |
The OS in UC cohort is reported. The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Adjusted Comparison of PFS by PD-L1 Status in UC Cohort in the Dose-expansion Phase |
The PFS by PD-L1 status in UC cohort is reported. The PFS estimates are adjusted for baseline eastern cooperative oncology (ECOG), smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The PFS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
|
| Secondary |
Adjusted Comparison of OS by PD-L1 Status in UC Cohort in the Dose-expansion Phase |
The OS by PD-L1 status in UC cohort is reported. The OS estimates are adjusted for baseline ECOG, smoking status, race, gender, age, previous lines of therapy, and liver metastasis. 95% CIs based on log (-log(survival)). The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. |
From Day 1 through disease progression, study withdrawal, or initiation of another anticancer therapy, whichever occurred first (approximately 5.25 years) |
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