Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase |
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Primary |
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase |
Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Primary |
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase |
Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Primary |
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase |
Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Primary |
Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase |
The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. 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. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase |
The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase |
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 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. The DCR at >= 8 weeks and >=24 weeks are reported. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase |
The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) 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 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. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase |
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 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 PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase |
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 PFS was estimated using Kaplan-Meier method. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Overall Survival in Dose-expansion Phase |
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 baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. 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% decrease 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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. 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. |
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified 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 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. The DCR at >= 8 weeks and >=24 weeks are reported. |
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified 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 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. |
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
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 modified 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 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 PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method. |
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase |
The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method. |
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
OS in Dose-escalation Phase |
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 baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) |
|
| Secondary |
Number of Participants With TEAEs and TESAEs in Dose-expansion Phase |
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase |
Number of participants in dose-expansion phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase |
Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase |
Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported. |
Day 1 through 90 days post end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase |
|
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
|
| Secondary |
Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1) |
|
From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase) |
|
| Secondary |
Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases |
Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. |
Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 |
|
| Secondary |
Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases |
Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. |
Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 |
|
| Secondary |
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases |
Number of participants with positive ADAs to MEDI0680 are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). |
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months) |
|
| Secondary |
Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases |
Number of participants with positive ADA to durvalumab are reported. 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. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). |
Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months) |
|
| Secondary |
ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase |
ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response 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. 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. |
From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) |
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