Select Advanced Malignancies, Kidney Cancer, Clear Cell Renal Cell Carcinoma
Conditions
Keywords
select advanced malignancies,, kidney cancer,, clear cell renal cell carcinoma
Brief summary
To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.
Detailed description
This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.
Interventions
BIOLOGICALMEDI0680
Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.
BIOLOGICALDurvalumab
Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.
BIOLOGICALNivolumab
Participants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Must be 18 years or older * Eastern Cooperative Oncology Group performance status of 0-1 * Adequate organ function * At least 1 prior line of therapy
Exclusion criteria
* Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study * Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment * Prior treatment with immunotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported. |
| 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 | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| OS in Dose-escalation Phase | From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant) | 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. |
| Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported. |
| 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) | — |
| 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) | — |
| Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 | 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. |
| Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 | 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. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | 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) | 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). |
| Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | 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) | 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). |
| ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Day 1 through 90 days post end of treatment (approximately 5 years 10 months) | 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. |
| Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
| Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months) | 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. |
Countries
Australia, Canada, France, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
The study is conducted in Australia, Canada, Europe and the USA.
Participants by arm
| Arm | Count |
|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg Q2W for up to 12 months. | 4 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. | 5 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. | 3 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. | 3 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. | 9 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months. | 6 |
| MEDI0680 20 mg/kg Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. | 4 |
| MEDI0680 20 mg/kg + Durvalumab 750 mg Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. | 42 |
| Nivolumab 240 mg Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first. | 21 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 1 | 2 | 5 | 1 | 2 | 9 | 4 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 1 | 0 | 0 | 0 | 2 | 3 | 1 | 28 | 15 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 2 | 1 | 2 | 2 | 1 | 4 | 2 |
Baseline characteristics
| Characteristic | MEDI0680 0.1 mg/kg + Durvalumab 3 mg | MEDI0680 0.1 mg/kg + Durvalumab 10 mg | MEDI0680 0.5 mg/kg + Durvalumab 10 mg | MEDI0680 2.5 mg/kg + Durvalumab 10 mg | MEDI0680 10 mg/kg + Durvalumab 10 mg | MEDI0680 20 mg/kg + Durvalumab 10 mg | MEDI0680 20 mg/kg | MEDI0680 20 mg/kg + Durvalumab 750 mg | Nivolumab 240 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 12.6 | 67.4 years STANDARD_DEVIATION 8.4 | 52.3 years STANDARD_DEVIATION 17.9 | 62.3 years STANDARD_DEVIATION 11.6 | 62.1 years STANDARD_DEVIATION 11 | 69.5 years STANDARD_DEVIATION 9.9 | 64.8 years STANDARD_DEVIATION 14.2 | 61.0 years STANDARD_DEVIATION 9.8 | 59.1 years STANDARD_DEVIATION 10.5 | 61.5 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 7 Participants | 6 Participants | 4 Participants | 40 Participants | 20 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 8 Participants | 6 Participants | 3 Participants | 34 Participants | 16 Participants | 80 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 2 Participants | 1 Participants | 9 Participants | 6 Participants | 29 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 33 Participants | 15 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 2 / 5 | 1 / 3 | 2 / 3 | 5 / 9 | 1 / 6 | 2 / 4 | 9 / 42 | 4 / 21 |
| other Total, other adverse events | 4 / 4 | 5 / 5 | 3 / 3 | 3 / 3 | 9 / 9 | 6 / 6 | 4 / 4 | 41 / 42 | 20 / 21 |
| serious Total, serious adverse events | 1 / 4 | 1 / 5 | 1 / 3 | 2 / 3 | 6 / 9 | 0 / 6 | 3 / 4 | 22 / 42 | 13 / 21 |
Outcome results
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 1 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 3 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 2 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | International normalized ratio | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lipase increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypercalcaemia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood urea increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood fibrinogen decreased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Leukocytosis | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Amylase increased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Activated partial thromboplastin time prolonged | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Alanine aminotransferase increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Iron deficiency anaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Gamma glutamyltransferase increased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | White blood cell count decreased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypokalaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyponatraemia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood creatinine increased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hypermagnesaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Prothrombin time prolonged | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphopenia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Lymphocyte count decreased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Anaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Blood phosphorus decreased | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | Hyperuricaemia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase | proteinuria | 0 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Tachycardia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Pericardial effusion | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 3 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Sinus tachycardia | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Palpitations | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Pyrexia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Weight decreased | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Tachycardia | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase | Hypertension | 1 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 4 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 5 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 1 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 3 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 9 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 6 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TEAE | 6 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase | Any TESAE | 0 Participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | 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 | 0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | 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 | 16.7 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | 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 | 23.8 Percentage of participants |
p-value: 0.549495% CI: [-72.8, 31.1]Fisher Exact
p-value: 0.51395% CI: [-33.6, 20]Fisher Exact
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
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: The study did not meet its primary endpoint of demonstrating superior antitumor effect of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy-naïve participants with advanced or metastatic ccRCC as assessed by the investigator using RECIST v1.1. Therefore, the decision was made not to perform the BICR analysis for antitumor activity and hence data were not collected.
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PD | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PR | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | NE | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | CR | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | SD | 3 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | CR | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PD | 17 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | SD | 17 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | NE | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PR | 5 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | NE | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PR | 5 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | SD | 8 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | PD | 6 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | CR | 0 Participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 1 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 1 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 1 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 2 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 1 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 3 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | SD | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PR | 4 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NE | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | PD | 1 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | CR | 0 Participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 75.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 50.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 20.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 0 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 33.3 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 33.3 Percentage of participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 33.3 Percentage of participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 0 Percentage of participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 66.7 Percentage of participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 44.4 Percentage of participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 8 weeks | 83.3 Percentage of participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | DCR at >= 24 weeks | 83.3 Percentage of participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=8 weeks | 75.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=24 weeks | 50.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=8 weeks | 57.1 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=24 weeks | 38.1 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=8 weeks | 61.9 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | DCR at >=24 weeks | 38.1 Percentage of participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: AAs-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The DoR was analyzed for those participants who achieved OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 16.8 Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NA Months |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 7.4 Months |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | NA 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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The DoR was analyzed for those participants who achieved OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | NA Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | NA 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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypokalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperkalaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypertriglyceridaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypocalcaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoglycaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | White blood cell count increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypomagnesaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Anaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyponatraemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Alanine aminotransferase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypophosphataemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Urine abnormality | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood thyroid stimulating hormone increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood urine present | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Aspartate aminotransferase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood iron decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood bilirubin increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutropenia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine phosphokinase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatinine increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood glucose increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood triglycerides increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | C-reactive protein increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutrophil count decreased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lipase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Transaminases increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypercalcaemia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperglycaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutropenia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperkalaemia | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood thyroid stimulating hormone increased | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypercalcaemia | 6 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypertriglyceridaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase increased | 3 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine phosphokinase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoalbuminaemia | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Prothrombin time prolonged | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatinine increased | 4 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypocalcaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Aspartate aminotransferase increased | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoglycaemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lymphocyte count decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Transaminases increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypokalaemia | 5 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | White blood cell count increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood alkaline phosphatase increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypomagnesaemia | 4 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood iron decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood glucose increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyponatraemia | 3 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood bilirubin increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood triglycerides increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypophosphataemia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Alanine aminotransferase increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lipase increased | 4 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Urine abnormality | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Anaemia | 6 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine increased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutrophil count decreased | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood urine present | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | C-reactive protein increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood urine present | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count decreased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine phosphokinase increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood triglycerides increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood thyroid stimulating hormone increased | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutropenia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood iron decreased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lymphocyte count decreased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Neutrophil count decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Platelet count increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Prothrombin time prolonged | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | White blood cell count increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Alanine aminotransferase increased | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase decreased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Amylase increased | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Aspartate aminotransferase increased | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood alkaline phosphatase increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood bilirubin increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatine increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood creatinine increased | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Blood glucose increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | C-reactive protein increased | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Lipase increased | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Transaminases increased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypercalcaemia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperglycaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyperkalaemia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypertriglyceridaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoalbuminaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypocalcaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypoglycaemia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypokalaemia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypomagnesaemia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hyponatraemia | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Hypophosphataemia | 3 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Urine abnormality | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase | Anaemia | 5 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Cardiac failure congestive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Angina pectoris | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Tachycardia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Cardiac failure congestive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Angina pectoris | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Cardiac failure congestive | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Angina pectoris | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 1 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Pyrexia | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypertension | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypotension | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight decreased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Tachycardia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypoxia | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight increased | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight increased | 3 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypertension | 5 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Tachycardia | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypotension | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Pyrexia | 9 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight decreased | 5 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypoxia | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypotension | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Atrial fibrillation | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Tachycardia | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Pyrexia | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight decreased | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypoxia | 1 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Hypertension | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase | Weight increased | 0 Participants |
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).
Time frame: 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)
Population: As-treated population included those participants who received durvalumab and grouped according to actual treatment received. The Number of participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 1 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | Persistent Positive | 2 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 2 Participants |
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).
Time frame: 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)
Population: As-treated population included those participants who received MEDI0680 and grouped according to actual treatment received. The Number of participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 2 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 2 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 2 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 0 Participants |
| MEDI0680 20 mg/kg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | ADA positive post-baseline | 2 Participants |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Persistent Positive | 0 Participants |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases | Transient Positive | 2 Participants |
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.
Time frame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TEAE | 4 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TESAE | 3 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TEAE | 42 Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TESAE | 22 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TEAE | 20 Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Number of Participants With TEAEs and TESAEs in Dose-expansion Phase | Any TESAE | 13 Participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 50.0 Percentage of participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 0 Percentage of participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 33.3 Percentage of participants |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 0 Percentage of participants |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 44.4 Percentage of participants |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 66.7 Percentage of participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. Participants with PD-L1 positive (\> 1% tumor cell membrane or \> 1% immune cell staining) and PD-L1 negative (\<= 1% tumor cell membrane and \<= 1% immune cell staining) were evaluated for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 positive | 0 Percentage of Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 negative | 0 Percentage of Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 positive | 40.0 Percentage of Participants |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 negative | 13.5 Percentage of Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 positive | 37.5 Percentage of Participants |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase | Participants with PD-L1 negative | 15.4 Percentage of Participants |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | OS in Dose-escalation Phase | 16.3 Months |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | OS in Dose-escalation Phase | NA Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | OS in Dose-escalation Phase | 14.7 Months |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | OS in Dose-escalation Phase | 7.9 Months |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | OS in Dose-escalation Phase | 12.8 Months |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | OS in Dose-escalation Phase | NA 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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Overall Survival in Dose-expansion Phase | 19.9 Months |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Overall Survival in Dose-expansion Phase | NA Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Overall Survival in Dose-expansion Phase | NA 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)
Time frame: 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)
Population: Per the Statistical Analysis Plan, the data for percent change from baseline in target lesion was to be presented using Spider plot analysis. Hence, numeric data were not collected for this outcome measure.
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 20.2 Months |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 1.7 Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 1.6 Months |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 1.8 Months |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 7.0 Months |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 23.4 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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | 5.5 Months |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | 3.6 Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | 3.6 Months |
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.
Time frame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Population: As-treated population included those participants who received durvalumab and grouped according to actual treatment received. The Number of participants Analyzed denotes the number of participants who had quantifiable and calculable serum samples at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 65.47 μg/mL | Geometric Coefficient of Variation 10.02 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 19.62 μg/mL | Geometric Coefficient of Variation 16.49 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 95.14 μg/mL | Geometric Coefficient of Variation 12.79 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 23.83 μg/mL | Geometric Coefficient of Variation 14.35 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 84.43 μg/mL | Geometric Coefficient of Variation 17.13 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 83.76 μg/mL | Geometric Coefficient of Variation 34.29 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 63.02 μg/mL | Geometric Coefficient of Variation 7.836 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 216.1 μg/mL | Geometric Coefficient of Variation 25.14 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 280.9 μg/mL | Geometric Coefficient of Variation 12.48 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 245.8 μg/mL | Geometric Coefficient of Variation 13.45 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 297.5 μg/mL | Geometric Coefficient of Variation 42.41 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 241.1 μg/mL | Geometric Coefficient of Variation 30.9 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 49.04 μg/mL | Geometric Coefficient of Variation 80.97 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 213.8 μg/mL | Geometric Coefficient of Variation 9.943 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 89.20 μg/mL | Geometric Coefficient of Variation 56 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 225.0 μg/mL | Geometric Coefficient of Variation 9.213 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 267.0 μg/mL | Geometric Coefficient of Variation 25.97 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 136.3 μg/mL | Geometric Coefficient of Variation 45.72 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 188.0 μg/mL | Geometric Coefficient of Variation 17.82 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 86.10 μg/mL | Geometric Coefficient of Variation 69.76 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 79.59 μg/mL | Geometric Coefficient of Variation 63.46 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 248.0 μg/mL | Geometric Coefficient of Variation 27.2 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 124.8 μg/mL | Geometric Coefficient of Variation 55.78 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 370.9 μg/mL | Geometric Coefficient of Variation 42.57 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 292.7 μg/mL | Geometric Coefficient of Variation 33.84 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 253.9 μg/mL | Geometric Coefficient of Variation 11.35 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 70.31 μg/mL | Geometric Coefficient of Variation 22 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 321.8 μg/mL | Geometric Coefficient of Variation 23.05 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 342.3 μg/mL | Geometric Coefficient of Variation 18.08 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 142.5 μg/mL | Geometric Coefficient of Variation 50.52 |
| MEDI0680 20 mg/kg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 258.1 μg/mL | Geometric Coefficient of Variation 28.36 |
| MEDI0680 20 mg/kg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 78.41 μg/mL | Geometric Coefficient of Variation 55.62 |
| MEDI0680 20 mg/kg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 186.9 μg/mL | Geometric Coefficient of Variation 33.42 |
| MEDI0680 20 mg/kg | Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
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.
Time frame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
Population: As-treated population included those participants who received MEDI0680 and grouped according to actual treatment received. The Number of participants Analyzed denotes the number of participants who had quantifiable and calculable serum samples at the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 1.143 μg/mL | Geometric Coefficient of Variation 22.7 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 5.420 μg/mL | Geometric Coefficient of Variation 21.61 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 1.645 μg/mL | Geometric Coefficient of Variation 49.08 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 3.515 μg/mL | Geometric Coefficient of Variation 145.9 |
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 4.330 μg/mL | Geometric Coefficient of Variation 26.18 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 3.835 μg/mL | Geometric Coefficient of Variation 25.3 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 0.9937 μg/mL | Geometric Coefficient of Variation 35.93 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 3.688 μg/mL | Geometric Coefficient of Variation 80.17 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 3.877 μg/mL | Geometric Coefficient of Variation 54.68 |
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 1.361 μg/mL | Geometric Coefficient of Variation 38.07 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 17.28 μg/mL | Geometric Coefficient of Variation 56.32 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 16.36 μg/mL | Geometric Coefficient of Variation 26.46 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 4.428 μg/mL | Geometric Coefficient of Variation 62.38 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 7.879 μg/mL | Geometric Coefficient of Variation 52.74 |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 20.52 μg/mL | Geometric Coefficient of Variation 26.26 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 18.67 μg/mL | Geometric Coefficient of Variation 12.88 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 87.78 μg/mL | Geometric Coefficient of Variation 20.69 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 31.81 μg/mL | Geometric Coefficient of Variation 4.48 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 69.28 μg/mL | Geometric Coefficient of Variation 24.76 |
| MEDI0680 2.5 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 92.07 μg/mL | Geometric Coefficient of Variation 17.72 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 272.4 μg/mL | Geometric Coefficient of Variation 24.62 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 46.87 μg/mL | Geometric Coefficient of Variation 559.4 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 348.1 μg/mL | Geometric Coefficient of Variation 27.78 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 155.7 μg/mL | Geometric Coefficient of Variation 24.2 |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 440.7 μg/mL | Geometric Coefficient of Variation 28.18 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 378.0 μg/mL | Geometric Coefficient of Variation 17.95 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 860.8 μg/mL | Geometric Coefficient of Variation 13.82 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day15 | 716.8 μg/mL | Geometric Coefficient of Variation 26.72 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day15 | 205.8 μg/mL | Geometric Coefficient of Variation 24.56 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 529.9 μg/mL | Geometric Coefficient of Variation 29.84 |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 20 mg/kg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 20 mg/kg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 936.1 μg/mL | Geometric Coefficient of Variation 24.91 |
| MEDI0680 20 mg/kg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 308.6 μg/mL | Geometric Coefficient of Variation 30.45 |
| MEDI0680 20 mg/kg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 668.8 μg/mL | Geometric Coefficient of Variation 21.04 |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle1 Day1 | NA μg/mL | — |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmin at Cycle2 Day1 | 253.9 μg/mL | Geometric Coefficient of Variation 52.11 |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle1 Day1 | 135.9 μg/mL | Geometric Coefficient of Variation 4007 |
| MEDI0680 20 mg/kg + Durvalumab 750 mg | Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases | Cmax at Cycle2 Day1 | 586.6 μg/mL | Geometric Coefficient of Variation 63.42 |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The TTR was analyzed for those participants who achieved OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 10 mg | Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | 1.8 Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase | 1.8 Months |
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.
Time frame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
Population: As-treated population included those participants who received any study drug (MEDI0680, durvalumab, or nivolumab) and grouped according to actual treatment received. The TTR was analyzed for those participants who achieved OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEDI0680 0.1 mg/kg + Durvalumab 3 mg | TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 2.6 Months |
| MEDI0680 0.5 mg/kg + Durvalumab 10 mg | TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 3.4 Months |
| MEDI0680 10 mg/kg + Durvalumab 10 mg | TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 3.5 Months |
| MEDI0680 20 mg/kg + Durvalumab 10 mg | TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase | 3.2 Months |