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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-000974-44 | EudraCT Number |
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COLUMBIA-1 is a Phase 1b/2 platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) alone and in combination with novel oncology therapies in first-line metastatic microsatellite-stable colorectal cancer (MSS-CRC).
COLUMBIA-1 is a Phase 1b/2, open-label, multicenter, randomized, multidrug platform study to evaluate the safety and efficacy of standard of care (FOLFOX plus bevacizumab) in combination with novel oncology therapies in patients with first-line metastatic MSS-CRC. The study is designed to concurrently evaluate potential novel combinations with clinical promise using a 2-part approach. Part 1 is a Phase 1b study of safety, and Part 2 is a Phase 2 study of efficacy and safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Experimental | Participants in Part 1 safety run-in arm (S1) will receive intravenous (IV) infusions of FOLFOX (5-fluorouracil [5-FU]: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met. |
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| Part 2 (C1): FOLFOX + Bevacizumab | Experimental | Participants in Part 2 control 1 arm (C1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met. |
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| Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Experimental | Participants in Part 2 experimental 1 arm (E1) will receive IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion will be met. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Durvalumab | Drug | Participants will receive IV infusion of durvalumab as stated in arm description. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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) |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Los Angeles | California | 90095 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39048638 | Derived | Segal NH, Tie J, Kopetz S, Ducreux M, Chen E, Dienstmann R, Hollebecque A, Reilley MJ, Elez E, Cosaert J, Cain J, Soo-Hoo Y, Hewson N, Cooper ZA, Kumar R, Tabernero J. COLUMBIA-1: a randomised study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab in metastatic microsatellite-stable colorectal cancer. Br J Cancer. 2024 Oct;131(6):1005-1013. doi: 10.1038/s41416-024-02796-3. Epub 2024 Jul 25. |
| Label | URL |
|---|---|
| CSP redacted | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
A total of 61 participants were randomized in this study of which 59 participants received treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 1 safety run-in arm (S1) received intravenous (IV) infusions of FOLFOX (5-fluorouracil [5-FU]: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 11, 2022 | Oct 6, 2023 |
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The study is designed to concurrently evaluate potential novel combinations with clinical promise using a 2-part approach.
Part 1 is a Phase 1b study of safety, and Part 2 is a Phase 2 study of efficacy and safety. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety outcomes in Part 1.
Following a screening period of up to 28 days, participants will be centrally assigned (Part 1) or randomized (Part 2) to one of the open study arms. In both study parts, study treatment may be administered until disease progression or any discontinuation criteria are met.
In Part 2, experimental arms may be closed early based on futility from results of a planned interim analysis for each study arm. In both parts, new experimental arms consisting of FOLFOX and bevacizumab plus novel agent(s) may be added based on emerging nonclinical and clinical data via protocol amendment.
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| Oleclumab | Drug | Participants will receive IV infusion of oleclumab as stated in arm description. |
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| FOLFOX | Drug | Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description. |
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| Bevacizumab | Drug | Participants will receive IV infusion of bevacizumab as stated in arm description. |
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| Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years) |
| 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) |
| 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) |
| First dose (Day 1) through end of study (approximately 2.8 years) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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 |
| 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) |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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) |
| Sacramento |
| California |
| 95817 |
| United States |
| Research Site | Ann Arbor | Michigan | 48109 | United States |
| Research Site | Las Vegas | Nevada | 89169 | United States |
| Research Site | New York | New York | 10065 | United States |
| Research Site | Canton | Ohio | 44718 | United States |
| Research Site | Providence | Rhode Island | 02903 | United States |
| Research Site | Chattanooga | Tennessee | 37404 | United States |
| Research Site | Nashville | Tennessee | 37203 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Charlottesville | Virginia | 22908 | United States |
| Research Site | Clayton | 3168 | Australia |
| Research Site | Heidelberg | 3084 | Australia |
| Research Site | Melbourne | 3000 | Australia |
| Research Site | Toronto | Ontario | M5G 1X6 | Canada |
| Research Site | Nantes | 44000 | France |
| Research Site | Villejuif | 94805 | France |
| Research Site | Barcelona | 08035 | Spain |
| Research Site | Barcelona | 08916 | Spain |
| Research Site | Madrid | 28027 | Spain |
| Research Site | Madrid | 28046 | Spain |
| SAP redacted | View source |
| CSR redacted | View source |
| FG001 | Part 2 (C1): FOLFOX + Bevacizumab | Participants in Part 2 control 1 arm (C1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| FG002 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| COMPLETED |
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| NOT COMPLETED |
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As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 1 safety run-in arm (S1) received intravenous (IV) infusions of FOLFOX (5-fluorouracil [5-FU]: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| BG001 | Part 2 (C1): FOLFOX + Bevacizumab | Participants in Part 2 control 1 arm (C1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| BG002 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Day 1 through 90 days after the last dose of study drug (approximately 2.8 years) |
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| 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). | The DLT evaluable population included all participants in Part 1 safety run-in who received the full prescribed dose of durvalumab and ≥ 75% of the prescribed number of doses of FOLFOX plus bevacizumab and the other novel oncology therapy and completed the safety follow-up through the DLT evaluation period or experienced any DLT. | Posted | Count of Participants | Participants | From Day 1 to 28 days after the first dose of novel oncology therapy (durvalumab and oleclumab) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.8 years) |
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| 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). | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Day 1 through 90 days after the last dose of study drug (approximately 2.8 years) |
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| 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. | Intent-to-treat (ITT) population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Randomization through end of study (approximately 2.6 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Number | 95% Confidence Interval | Percentage of Participants | First dose (Day 1) through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | First dose (Day 1) through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. The DoR was assessed for only those participants who had OR. | Posted | Median | 95% Confidence Interval | Months | First dose (Day 1) through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Number | 95% Confidence Interval | Percentage of Participants | First dose (Day 1) through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Median | 95% Confidence Interval | Months | Assignment through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Assignment through 12 months |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Median | 95% Confidence Interval | Months | First dose (Day 1) through end of study (approximately 2.8 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Day 1 through 90 days after the last dose of study drug (approximately 2.6 years) |
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| 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. | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. Here, number analyzed (n) denotes number of participants analyzed for the specified parameter. | Posted | Count of Participants | Participants | Baseline (Day 1) through 90 days after the last dose of study drug (approximately 2.6 years) |
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| 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). | As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Day 1 through 90 days after the last dose of study drug (approximately 2.6 years) |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Count of Participants | Participants | Randomization through end of study (approximately 2.6 years) |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. The DoR was assessed for only those participants who had OR. | Posted | Median | 95% Confidence Interval | Months | Randomization through end of study (approximately 2.6 years) |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Randomization through end of study (approximately 2.6 years) |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Median | 95% Confidence Interval | Months | Randomization through end of study (approximately 2.6 years) |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Randomization through 12 months |
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| 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. | The ITT population included participants who received any study drug and were analyzed according to the treatment group they were randomized to. | Posted | Median | 95% Confidence Interval | Months | Randomization through end of study (approximately 2.6 years) |
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| 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. | Pharmacokinetic (PK) evaluable population included participants who received at least 1 dose of any study drug with at least 1 reportable PK concentration. Here, number of participants analyzed denotes those participants who were analyzed for this outcome measure. Number analyzed (n) denotes those participants who had adequate serum samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 |
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| 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. | The PK evaluable population included participants who received at least 1 dose of any study drug with at least 1 reportable PK concentration. Here, number of participants analyzed denotes those participants who were analyzed for this outcome measure. Number analyzed (n) denotes those participants who had adequate serum samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | 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 |
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| 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. | The PK evaluable population included participants who received at least 1 dose of any study drug with at least 1 reportable PK concentration. Here, number analyzed denotes those participants who had adequate serum samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose on Day 1 of Cycle 1, 2, 7, 13, and 27 |
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| 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. | The ADA evaluable population included all participants who received at least 1 dose of any study drug, who have a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who had adequate ADA sample. | Posted | Count of Participants | Participants | 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) |
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| 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. | The ADA evaluable population included all participants who received at least 1 dose of any study drug, who have a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who had adequate ADA sample. | Posted | Count of Participants | Participants | 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) |
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| 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. | The ADA evaluable population included all participants who received at least 1 dose of any study drug, who have a non-missing baseline ADA result and at least 1 non-missing post-baseline ADA result. Here, number analyzed (n) denotes those participants who had adequate ADA sample. | Posted | Count of Participants | Participants | 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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Part 1: Day 1 through 90 days after the last dose of study drug (approximately 2.8 years); Part 2: Day 1 through 90 days after the last dose of study drug (approximately 2.6 years)
As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 1 safety run-in arm (S1) received intravenous (IV) infusions of FOLFOX (5-fluorouracil [5-FU]: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg every 4 weeks (Q4W) and IV oleclumab 3000 mg every 2 weeks (Q2W) till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. | 4 | 7 | 1 | 7 | 7 | 7 |
| EG001 | Part 2 (C1): FOLFOX + Bevacizumab | Participants in Part 2 control 1 arm (C1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) in combination with IV bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. | 8 | 26 | 7 | 26 | 25 | 26 |
| EG002 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. | 13 | 26 | 12 | 26 | 26 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ventricular tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
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| Lumbar radiculopathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
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| Pyelocaliectasis | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Intestinal perforation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Large intestine perforation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
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| Cholangitis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
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| Covid-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Covid-19 pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Peritonitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Rectal abscess | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
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| Stoma complication | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Amylase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| International normalised ratio increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Lipase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 25.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Increased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Visual acuity reduced | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary hesitation | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Aphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Miliaria | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rectal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Crepitations | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Anorectal infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Covid-19 | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Diarrhoea infectious | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Medical device site infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 25.1 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Wound complication | Injury, poisoning and procedural complications | MedDRA 25.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 25.1 | Systematic Assessment |
|
The data cut-off for the study was October 2022. The decision was made to end recruitment for the study because superior efficacy was not observed for the novel study drug combinations under investigation. For patient that were benefiting from the treatment the study remained active for them to continue receiving treatment.
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca Clinical study Information Center | +1-877-240-9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 23, 2022 | Oct 6, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613593 | durvalumab |
| C410216 | Folfox protocol |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
| Counts |
|---|
| Participants |
|
|
|
| OG001 |
| Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
|
|
|
|
|
|
| OG001 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
| OG001 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
| OG001 | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met.
|
|
|
| Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
Participants in Part 2 experimental 1 arm (E1) received IV infusions of FOLFOX (5-FU: 2400 mg/m^2 over 46-48 hours [Day 1 and 2 of every 14-day Cycle], oxaliplatin: 85 mg/m^2, folinic acid: 400 mg/m^2) and bevacizumab 5 mg/kg on Day 1 of every Cycle (14-day cycle) in combination with IV durvalumab 1500 mg Q4W and IV oleclumab 3000 mg Q2W till 4 doses (Cycle 4) then Q4W starting on Cycle 5 Day 1 until disease progression, unacceptable toxicity, withdrawal of participant consent, or another discontinuation criterion was met. |
|
|
|