Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736, Durvalumab
Brief summary
This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.
Detailed description
The study will comprise of 6 parts. Participants in Part 1A (safety run-in cohort), Part 1B (efficacy-gating cohort), Part 2A, and Part 4 will receive weight-based dosing regimens; and participants in Part 2B and Part 3 will receive fixed dosing regimens. Part 1A Stage 2 of the study may start after the first 3 participants in Stage 1 have been observed on study for at least 4 weeks. In addition, a separate cohort of participants will be enrolled in mainland China (China cohort) once global recruitment in Part 2A will be closed. * In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous (IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W. * In Part 2A, participants will be randomized in a 1:1:1 ratio to receive: * Durvalumab 20 mg/kg Q4W * Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W) * Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by durvalumab 20 mg/kg Q4W * In China cohort, Part 2A study design will be followed. * In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W. * In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive: * Durvalumab 1500 mg Q4W * Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W * Tremelimumab 750 mg Q4W for 7 doses followed by Q12W * Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab 1500 mg Q4W. Following protocol amendment 5, enrollment into 'Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg' arm will close. Participants will be randomized at a ratio of 2:1:2 in 'Durvalumab 1500 mg Q4W', 'Tremelimumab 750 mg Q4W for 7 doses followed by Q12W', and 'Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W' arms, respectively. • In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg every 3 weeks (Q3W). Participants will receive the treatment until confirm progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. All participants will be followed for survival until the end of study visit (last participant discontinues the study treatment).
Interventions
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
Bevacizumab 15 mg/kg will be administered by IV infusion every 3 weeks until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first.
Sponsors
Study design
Eligibility
Inclusion criteria
1. Male or female participants 2. 18 years and older (Japan-20 years and older) 3. Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods. 4. Immunotherapy-naïve 5. Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.
Exclusion criteria
1. Prior exposure to immune-mediated therapy 2. Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy 3. Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months 4. Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. 5. Main portal vein thrombosis (Vp4) as documented on imaging 6. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment 7. Active or prior documented autoimmune or inflammatory disease with some exceptions 8. Current or prior use of immunosuppressive medication within 14 days with some exceptions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | From Day 1 to Day 28 after first dose of study drug | A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any \>= Grade 2 pneumonitis that does not resolve to \<= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to \<= Grade 1 or baseline within 14 days, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN, aspartate aminotransferase or alanine aminotransferase \> 3 × ULN with concurrent increase in total bilirubin \> 2 × ULN without evidence of cholestasis or alternative explanations, and any \>= Grade 3 non-irAE (except for the protocol stated conditions). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study. |
| Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study. |
| Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Disease assessments based on investigator assessments and BICR review were determined by using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) guidelines. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. There will be no updated results for this outcome measure at the time of end of study. |
| Disease Control Rate (DCR) Based on Investigator Assessments and BICR | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The DCR is defined as a BOR of confirmed CR, confirmed PR, or stable disease (SD). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (\>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. There will be no updated results for this outcome measure at the time of end of study. |
| Time to Response (TTR) Based on Investigator Assessments and BICR | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTR is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (\>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
| Duration of Response (DoR) Based on Investigator Assessments and BICR | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | The DoR is defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments and BICR review by using RECIST v1.1 or death in absence of disease progression. A confirmed CR is defined in above outcome measures. The PD is defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. The DoR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
| Time to Progression (TTP) Based on Investigator Assessments and BICR | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTP was defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 to the first documentation of radiographic disease progression. However, if the participant died without tumor progression, they were censored at the time of death. Participants with no documented PD by the data cutoff date for TTP analysis were censored at the date of their last evaluable disease assessment. The TTP was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
| Progression Free Survival (PFS) Based on Investigator Assessments and BICR | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The PFS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of radiographic disease progression or death due to any cause, whichever occurs first. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared with the nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. Participants who were alive with no documented PD by the data cutoff date for PFS analysis were censored at the date of their last evaluable disease assessment. The PFS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
| Overall Survival (OS) | From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months) | The OS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until death due to any cause. If there was no death reported for a participant by the data cut-off date for overall survival analysis, OS was censored at the last known alive date. The OS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study. |
Countries
China, Hong Kong, Italy, Japan, Singapore, South Korea, Spain, Taiwan, United States
Contacts
MedImmune LLC
Participant flow
Pre-assignment details
The results data are reported per the primary completion date (data cut-off date of 06Nov2020).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg Participants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) received tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 40 |
| Parts 2 and 3: Durvalumab 1500 mg Participants received durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 104 |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg Participants received tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurred first. | 75 |
| Parts 2 and 3: Tremelimumab 750 mg Participants received tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 69 |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg Participants received tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 84 |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg Participants received durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 47 |
| China Cohort: Durvalumab 20 mg/kg Participants received durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 3 |
| China Cohort: Tremelimumab 10 mg/kg Participants received tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 5 |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg Participants received tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first. | 6 |
| Total | 433 |
Baseline characteristics
| Characteristic | Total | Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Parts 2 and 3: Durvalumab 1500 mg | Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Parts 2 and 3: Tremelimumab 750 mg | Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | China Cohort: Durvalumab 20 mg/kg | China Cohort: Tremelimumab 10 mg/kg | China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >=65 to < 75 years | 130 Participants | 8 Participants | 33 Participants | 31 Participants | 18 Participants | 26 Participants | 13 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized < 65 years | 241 Participants | 27 Participants | 52 Participants | 34 Participants | 41 Participants | 48 Participants | 26 Participants | 3 Participants | 5 Participants | 5 Participants |
| Age, Customized > 75 years | 62 Participants | 5 Participants | 19 Participants | 10 Participants | 10 Participants | 10 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 412 Participants | 38 Participants | 99 Participants | 71 Participants | 65 Participants | 79 Participants | 47 Participants | 3 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 257 Participants | 19 Participants | 55 Participants | 44 Participants | 39 Participants | 47 Participants | 39 Participants | 3 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 3 Participants | 10 Participants | 4 Participants | 2 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 140 Participants | 15 Participants | 35 Participants | 27 Participants | 26 Participants | 30 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 65 Participants | 10 Participants | 12 Participants | 10 Participants | 12 Participants | 14 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 368 Participants | 30 Participants | 92 Participants | 65 Participants | 57 Participants | 70 Participants | 41 Participants | 2 Participants | 5 Participants | 6 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 | 31 / 40 | 78 / 104 | 49 / 75 | 55 / 69 | 64 / 84 | 18 / 47 | 2 / 3 | 5 / 5 | 5 / 6 |
| other Total, other adverse events | 37 / 40 | 92 / 101 | 73 / 74 | 66 / 69 | 80 / 82 | 45 / 47 | 3 / 3 | 5 / 5 | 5 / 5 |
| serious Total, serious adverse events | 22 / 40 | 45 / 101 | 32 / 74 | 36 / 69 | 37 / 82 | 17 / 47 | 1 / 3 | 3 / 5 | 4 / 5 |
Outcome results
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 2 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 6 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 4 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 4 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 4 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 6 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 4 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 14 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 4 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 4 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 9 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 4 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 2 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 4 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 2 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 2 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 14 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 6 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 2 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 4 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 1 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 2 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 2 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypertension | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Palpitations | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Pyrexia | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Hypotension | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight increased | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Systolic hypertension | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Abnormal Vital Signs Reported as TEAEs | Weight decreased | 1 Participants |
Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Safety analysis set included all participants who received at least one dose of study drug. 'Number of participants analyzed' denotes only those participants for whom hematological and clinical chemistry parameter were analyzed. 'Number Analyzed' denotes the participants analyzed for the specified laboratory parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 9 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 3 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 2 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 2 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 4 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 5 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 2 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 2 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 4 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 3 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 3 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 3 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 5 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 2 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 5 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 7 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 7 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 25 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 13 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 2 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 12 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 5 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 5 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 4 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 5 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 2 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 12 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 4 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 7 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 2 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 8 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 13 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 3 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 4 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 3 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 5 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 3 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 6 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 7 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 4 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 2 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 10 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 14 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 2 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 19 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 6 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 13 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 6 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 4 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 16 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 6 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 5 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 3 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 6 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 2 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 2 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 2 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 2 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 5 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 5 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 4 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 10 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 11 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 2 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 9 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 6 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 17 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 8 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 2 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 8 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 6 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 3 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 4 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 2 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 2 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 2 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 3 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 3 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 2 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 1 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 1 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 1 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 1 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Bilirubin | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hypo | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Aspartate Aminotransferase | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Sodium - Hypo | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Neutrophils | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Activated Partial Thromboplastin Time | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Hemoglobin | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alkaline Phosphatase | 1 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Lymphocytes | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Platelets | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Albumin | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Alanine Aminotransferase | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Creatinine | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Leukocytes | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Prothrombin Intl. Normalized Ratio | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Magnesium - Hypo | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Fibrinogen | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Calcium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Potassium - Hyper | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters | Glucose - Hyper | 0 Participants |
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any \>= Grade 2 pneumonitis that does not resolve to \<= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to \<= Grade 1 or baseline within 14 days, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN, aspartate aminotransferase or alanine aminotransferase \> 3 × ULN with concurrent increase in total bilirubin \> 2 × ULN without evidence of cholestasis or alternative explanations, and any \>= Grade 3 non-irAE (except for the protocol stated conditions).
Time frame: From Day 1 to Day 28 after first dose of study drug
Population: DLT evaluable set included all Part 1A participants who received at least 1 dose of study drug and completed the safety follow-up through the DLT evaluation period (Days 1 to 28 after first dose of study drug) or experienced any DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 1 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 1 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 1 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 1 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 3 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 1 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 2 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 1 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 1 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 0 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Coronary artery disease | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Sinus bradycardia | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure congestive | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac arrest | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrioventricular block first degree | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Acute myocardial infarction | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina pectoris | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Atrial fibrillation | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Angina unstable | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Myocardial infarction | 0 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events | Cardiac failure chronic | 0 Participants |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Safety analysis set included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 38 Participants |
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 22 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 95 Participants |
| Parts 2 and 3: Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 45 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 73 Participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 32 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 67 Participants |
| Parts 2 and 3: Tremelimumab 750 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 36 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 80 Participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 37 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 17 Participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 45 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 1 Participants |
| China Cohort: Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 3 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 5 Participants |
| China Cohort: Tremelimumab 10 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 3 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 5 Participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 4 Participants |
Disease Control Rate (DCR) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The DCR is defined as a BOR of confirmed CR, confirmed PR, or stable disease (SD). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (\>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 60.0 Percentage of participants |
| Parts 2 and 3: Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 45.2 Percentage of participants |
| Parts 2 and 3: Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on BICR | 37.5 Percentage of participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 50.7 Percentage of participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on BICR | 45.3 Percentage of participants |
| Parts 2 and 3: Tremelimumab 750 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on BICR | 49.3 Percentage of participants |
| Parts 2 and 3: Tremelimumab 750 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 47.8 Percentage of participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 34.5 Percentage of participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on BICR | 36.9 Percentage of participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on BICR | 55.3 Percentage of participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 63.8 Percentage of participants |
| China Cohort: Durvalumab 20 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 33.3 Percentage of participants |
| China Cohort: Tremelimumab 10 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 20.0 Percentage of participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Disease Control Rate (DCR) Based on Investigator Assessments and BICR | DCR based on Investigator assessments | 16.7 Percentage of participants |
Duration of Response (DoR) Based on Investigator Assessments and BICR
The DoR is defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments and BICR review by using RECIST v1.1 or death in absence of disease progression. A confirmed CR is defined in above outcome measures. The PD is defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. The DoR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed. The DoR was analyzed for participants who achieved OR per BICR and/or investigator assessments. 'Number Analyzed' denotes participants who achieved OR.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 16.66 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on BICR | 14.95 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | NA Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on BICR | 18.43 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 23.95 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on BICR | 23.95 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 27.53 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on BICR | 13.21 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 13.21 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on BICR | NA Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 10.51 Months |
| China Cohort: Durvalumab 20 mg/kg | Duration of Response (DoR) Based on Investigator Assessments and BICR | DoR based on Investigator assessments | 7.39 Months |
Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR)
Disease assessments based on investigator assessments and BICR review were determined by using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) guidelines. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 20.0 Percentage of participants |
| Parts 2 and 3: Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 11.5 Percentage of participants |
| Parts 2 and 3: Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on BICR | 11.5 Percentage of participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 21.3 Percentage of participants |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on BICR | 24.0 Percentage of participants |
| Parts 2 and 3: Tremelimumab 750 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on BICR | 7.2 Percentage of participants |
| Parts 2 and 3: Tremelimumab 750 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 8.7 Percentage of participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 8.3 Percentage of participants |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on BICR | 9.5 Percentage of participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on BICR | 21.3 Percentage of participants |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 34.0 Percentage of participants |
| China Cohort: Durvalumab 20 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | 33.3 Percentage of participants |
| China Cohort: Tremelimumab 10 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | NA Percentage of participants |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR) | ORR based on Investigator assessments | NA Percentage of participants |
Overall Survival (OS)
The OS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until death due to any cause. If there was no death reported for a participant by the data cut-off date for overall survival analysis, OS was censored at the last known alive date. The OS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Overall Survival (OS) | 12.58 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Overall Survival (OS) | 12.91 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Overall Survival (OS) | 17.05 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Overall Survival (OS) | 17.05 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Overall Survival (OS) | 11.30 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Overall Survival (OS) | NA Months |
| China Cohort: Durvalumab 20 mg/kg | Overall Survival (OS) | 30.69 Months |
| China Cohort: Tremelimumab 10 mg/kg | Overall Survival (OS) | 3.52 Months |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Overall Survival (OS) | 6.28 Months |
Progression Free Survival (PFS) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The PFS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of radiographic disease progression or death due to any cause, whichever occurs first. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared with the nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. Participants who were alive with no documented PD by the data cutoff date for PFS analysis were censored at the date of their last evaluable disease assessment. The PFS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 3.52 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 2.40 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on BICR | 2.07 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 3.52 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on BICR | 2.17 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on BICR | 2.69 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 2.60 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 1.81 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on BICR | 1.87 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on BICR | 4.17 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 6.24 Months |
| China Cohort: Durvalumab 20 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 1.81 Months |
| China Cohort: Tremelimumab 10 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 2.20 Months |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Progression Free Survival (PFS) Based on Investigator Assessments and BICR | PFS based on Investigator assessments | 1.87 Months |
Time to Progression (TTP) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTP was defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 to the first documentation of radiographic disease progression. However, if the participant died without tumor progression, they were censored at the time of death. Participants with no documented PD by the data cutoff date for TTP analysis were censored at the date of their last evaluable disease assessment. The TTP was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 3.68 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 3.38 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on BICR | 2.10 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 3.68 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on BICR | 3.71 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on BICR | 2.76 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 2.60 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 1.87 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on BICR | 1.87 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on BICR | 4.30 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 7.46 Months |
| China Cohort: Durvalumab 20 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 1.81 Months |
| China Cohort: Tremelimumab 10 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 3.75 Months |
| China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Time to Progression (TTP) Based on Investigator Assessments and BICR | TTP based on Investigator assessments | 2.68 Months |
Time to Response (TTR) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTR is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (\>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Population: Full analysis set included all randomized participants (Parts 2A and 3) or participants who were allocated to treatment (Parts 1, 2B, and 4), including participants who were randomized in error. Analysis of disease assessments based on BICR for Part 1 and China cohorts were not planned and hence not performed. The TTR was analyzed for participants who achieved OR per BICR and/or investigator assessments. 'Number Analyzed' denotes participants who achieved OR.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 2.68 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on BICR | 3.65 Months |
| Parts 2 and 3: Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 3.68 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on BICR | 2.28 Months |
| Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 1.86 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on BICR | 1.81 Months |
| Parts 2 and 3: Tremelimumab 750 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 2.74 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on BICR | 2.86 Months |
| Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 3.88 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on BICR | 2.10 Months |
| Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 2.10 Months |
| China Cohort: Durvalumab 20 mg/kg | Time to Response (TTR) Based on Investigator Assessments and BICR | TTR based on Investigator assessments | 5.55 Months |