Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part 1 |
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. |
Day 1 through 90 days after the last dose of study drug (approximately 2.8 years) |
|
| Primary |
Number of Participants With Dose Limiting Toxicities (DLTs) in Part 1 |
DLT: Any study drug related Grade (G)3 or higher toxicity including: any G3/G4 immune-mediated AE, any G3/4 noninfectious pneumonitis/colitis, transaminase elevation (TE) >8x upper limit of normal (ULN) or total bilirubin (TBL) >5xULN, increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=3xULN along with TBL >=2xULN, isolated liver TE >5 but =<8xULN or isolated TBL >3 but =<5xULN that does not downgrade to G1 or less within 14 days of onset, G3 nausea/vomiting/diarrhea that does not resolve to G2 or less within 3 days of maximal supportive care (MSC), G3/4 febrile neutropenia, G3/4 neutropenia not associated with fever/systemic infection, G4 anemia, G3 anemia with clinical sequelae/requires >2 units of red blood cells transfusion, thrombocytopenia (G4 >=7 days, G3 that did not improve by at least 1 grade within 7 days, G3/4 associated with G3/higher hemorrhage). |
From Day 1 to 28 days after the first dose of novel oncology therapy (durvalumab and oleclumab) |
|
| Primary |
Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 1 |
Number of participants with at least common terminology criteria for adverse events (CTCAE v5.0) 2-grade shift from baseline (last assessment prior to first dose) to worst toxicity grade in clinical laboratory parameters are reported. Clinical laboratory parameter analysis included hematology, clinical chemistry, coagulation, and urinalysis. |
Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years) |
|
| Primary |
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 1 |
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, and pulse rate). |
Day 1 through 90 days after the last dose of study drug (approximately 2.8 years) |
|
| Primary |
Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in Part 2 |
The OR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 criteria. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesion. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
Percentage of Participants With OR Per RECIST v1.1 in Part 1 |
The OR is defined as BOR of confirmed CR or confirmed PR based on RECIST v1.1 criteria. The CR is defined as disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. |
First dose (Day 1) through end of study (approximately 2.8 years) |
|
| Secondary |
Best Overall Response (BOR) Per RECIST v1.1 in Part 1 |
BOR: best response including CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) among all overall responses based on application of RECIST v1.1 to investigator assessments. CR: disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis <10 mm, and no new lesions. PR: at least 30% decrease in the SoD of TL (compared to baseline) and no new NTL. Confirmation of CR and PR is required after 4 weeks. PD: at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5mm, or unequivocal progression of existing NTL, or new lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD in at least 8 weeks from first dose of study drug. NE: either when no or only a subset of lesion measurements are made at an assessment. Number of participants with BOR are reported. |
First dose (Day 1) through end of study (approximately 2.8 years) |
|
| Secondary |
Duration of Response (DoR) Per RECIST v1.1 in Part 1 |
The DoR is defined as the time from the first documentation of a confirmed response (CR or PR) until the first documentation of PD or death due to any cause, whichever occurs first. The CR is defined as disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesion. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The DoR was analyzed using Kaplan-Meier method. |
First dose (Day 1) through end of study (approximately 2.8 years) |
|
| Secondary |
Percentage of Participants With Disease Control (DC) Per RECIST v1.1 in Part 1 |
The DC is defined as BOR of confirmed CR, confirmed PR, or stable disease (SD; maintained for = 16 weeks) per RECIST v1.1. The CR is defined as disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesion. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Participants with SD will be included in the DC if they maintain SD for >= 16 weeks from start of treatment. |
First dose (Day 1) through end of study (approximately 2.8 years) |
|
| Secondary |
Progression-Free Survival (PFS) Per RECIST v1.1 in Part 1 |
The PFS is defined as the time from assignment until the first documentation of PD or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer therapy prior to progression. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The PFS was analyzed using the Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. Assignment occurred between Day -3 and -1. |
Assignment through end of study (approximately 2.8 years) |
|
| Secondary |
Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 1 |
The PFS is defined as the time from assignment until the first documentation of PD or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer therapy prior to progression. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The PFS was analyzed using Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. The percentage of participants progression free and alive at 12 months (PFS-12) are reported. Assignment occurred between Day -3 and -1. |
Assignment through 12 months |
|
| Secondary |
Overall Survival (OS) Per RECIST v1.1 in Part 1 |
The OS is defined as the time from first dose until death due to any cause. The overall survival was analyzed using the Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. |
First dose (Day 1) through end of study (approximately 2.8 years) |
|
| Secondary |
Number of Participants With TEAEs and TESAEs in Part 2 |
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
Day 1 through 90 days after the last dose of study drug (approximately 2.6 years) |
|
| Secondary |
Number of Participants With at Least 2-Grade Shift From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters in Part 2 |
Number of participants with at least CTCAE v5.0 2-grade shift from baseline (last assessment prior to first dose) to worst toxicity grade in clinical laboratory parameters are reported. Clinical laboratory parameter analysis included hematology, clinical chemistry, coagulation, and urinalysis. |
Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.6 years) |
|
| Secondary |
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part 2 |
Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, blood pressure, and pulse rate). |
Day 1 through 90 days after the last dose of study drug (approximately 2.6 years) |
|
| Secondary |
BOR Per RECIST v1.1 in Part 2 |
BOR: best response including CR, PR, SD, PD, NE among all overall responses based on application of RECIST v1.1 to investigator assessments. CR: disappearance of all TLs, NTLs, normalization of tumor marker level, any pathological lymph nodes (target, non-target) must have reduction in short axis <10 mm, no new lesions. PR: at least 30% decrease in the SoD of TL (compared to baseline) and no new NTL. Confirmation of CR, PR is required after 4 weeks. PD: at least a 20% increase in SoDs of TLs, taking as reference smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD in at least 8 weeks from first dose of study drug. NE: either when no or only a subset of lesion measurements are made at an assessment. Number of participants with BOR are reported. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
DoR Per RECIST v1.1 in Part 2 |
The DoR is defined as the time from the first documentation of a confirmed response (CR or PR) until the first documentation of PD or death due to any cause, whichever occurs first. The CR is defined as disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesion. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The DoR was analyzed using Kaplan-Meier method. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
Percentage of Participants With DC Per RECIST v1.1 in Part 2 |
The DC is defined as BOR of confirmed CR, confirmed PR, or SD (maintained for = 16 weeks) per RECIST v1.1. The CR is defined as disappearance of all TLs and NTLs, normalization of tumor marker level, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesion. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Participants with SD will be included in the DC if they maintain SD for >= 16 weeks from start of treatment. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
PFS Per RECIST v1.1 in Part 2 |
The PFS is defined as the time from randomization until the first documentation of PD or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer therapy prior to progression. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The PFS was analyzed using the Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 2 |
The PFS is defined as the time from randomization until the first documentation of PD or death due to any cause, whichever occurs first, regardless of whether the participant received subsequent anticancer therapy prior to progression. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing NTL, or new lesions. The PFS was analyzed using Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. The percentage of participants progression free and alive at 12 months (PFS-12) are reported. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through 12 months |
|
| Secondary |
OS Per RECIST v1.1 in Part 2 |
The OS is defined as the time from randomization until death due to any cause. The overall survival was analyzed using the Kaplan-Meier method based on application of RECIST v1.1 to investigator assessments. In Part 2, randomization occurred between Day -8 and the same date as dosing. |
Randomization through end of study (approximately 2.6 years) |
|
| Secondary |
Serum Concentrations of Durvalumab in Part 1 (S1) and Part 2 (E1) |
Serum concentrations of durvalumab collected over time in Part 1 (S1) and Part 2 (E1) are reported. The lower limit of quantification (LLOQ) for durvalumab was considered to be 50 ng/mL. |
Part 1: Pre-dose on Day 1 of Cycle 1, 3, 7, 13; Part 2 (E1): Pre-dose on Day 1 of Cycle 1, 3, 7, 13, and 27 |
|
| Secondary |
Serum Concentrations of Oleclumab in Part 1 (S1) and Part 2 (E1) |
Serum concentrations of oleclumab collected over time in Part 1 (S1) and Part 2 (E1) are reported. The LLOQ for oleclumab was considered to be 1 µg/mL. |
Part 1: Pre-dose on Day 1 of Cycle 1, 2, 7, and 13; Part 2 (E1): Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27 |
|
| Secondary |
Serum Concentrations of Bevacizumab in Part 1 (S1) |
Serum concentrations of bevacizumab collected over time in Part 1 (S1) are reported. The LLOQ for bevacizumab was considered to be 500 ng/mL. |
Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27 |
|
| Secondary |
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab in Part 1 (S1) and Part 2 (E1) |
Number of participants with positive ADA to durvalumab in Part 1 (S1) and Part 2 (E1) are reported. |
Part 1: Pre-dose on Day(D)1 of Cycles(C)1 (baseline [BL]), 3, 7, 13, and 90 days post last dose of study drug (approximately 2.8 years); Part 2(E1):Pre-dose on D1 of C1 (BL), 3, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.6 years) |
|
| Secondary |
Number of Participants With Positive ADA to Oleclumab in Part 1 (S1) and Part 2 (E1) |
Number of participants with positive ADA to oleclumab in Part 1 (S1) and Part 2 (E1) are reported. |
Part 1: Pre-dose on D1 of C1 (BL), 2, 7, 13, and 90 days post last dose of study drug (approximately 2.8 years); Part 2 (E1): Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.6 years) |
|
| Secondary |
Number of Participants With Positive ADA to Bevacizumab in Part 1 (S1) |
Number of participants with positive ADA to bevacizumab in Part 1 (S1) are reported. |
Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.8 years) |
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