A Phase 1/2 interventional study of Durvalumab and Oleclumab in Metastatic Microsatellite-stable Colorectal Cancer, sponsored by MedImmune LLC. Active, not recruiting at 21 sites in 5 countries. Open to participants aged 18 Years to 101 Years. Per ClinicalTrials.gov, last updated 2026-08-11.
Sponsored by MedImmune LLC (part of AstraZeneca) · Phase 1/2, Interventional, and Treatment
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.
2,457 studies on the registry are indexed under Colonic Neoplasms; 458 are open to participants now.
This study's enrollment of 61 is below the median of 75 across 1,711 interventional studies indexed under Colonic Neoplasms.
Browse Colonic Neoplasms studies →MedImmune LLC is the lead sponsor of 270 studies on the registry; none are open to participants now.
Of its 52 completed or terminated interventional studies of FDA-regulated products, 29 (56%) have results posted.
First submitted after MedImmune LLC became part of AstraZeneca.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Durvalumab · Drug: Oleclumab · Drug: FOLFOX · Drug: Bevacizumab
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.
Drug: FOLFOX · Drug: Bevacizumab
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.
Drug: Durvalumab · Drug: Oleclumab · Drug: FOLFOX · Drug: Bevacizumab
Participants will receive IV infusion of durvalumab as stated in arm description.
Also known as: MEDI4736
Participants will receive IV infusion of oleclumab as stated in arm description.
Also known as: MEDI9447
Participants will receive IV infusion of FOLFOX (5-FU, oxaliplatin, and folinic acid) as stated in arm description.
Participants will receive IV infusion of bevacizumab as stated in arm description.
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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: Randomization through end of study (approximately 2.6 years)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Pre-dose on D1 of C1 (BL), 2, 7, 13, 27, and 90 days post last dose of study drug (approximately 2.8 years)
| Milestone | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|---|
| Started | 7 | 26 | 26 |
| Completed | 0 | 0 | 0 |
| Not completed | 7 | 26 | 26 |
| Withdrew: Death | 4 | 8 | 13 |
| Withdrew: Lost to follow-up | 0 | 2 | 0 |
| Withdrew: Withdrawal by subject | 0 | 4 | 2 |
| Withdrew: Other | 3 | 12 | 11 |
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.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Any TEAE | 7 |
| Any TESAE | 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).
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) in Part 1 | 0 |
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.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Hemoglobin (Hypo) | 1 |
| Lymphocytes (Hypo) | 2 |
| Neutrophils | 4 |
| Leukocytes (Hypo) | 3 |
| Activated Partial Thromboplastin Time | 1 |
| Albumin | 1 |
| Amylase | 2 |
| Bilirubin | 1 |
| Calcium Corrected (Hypo) | 1 |
| Creatine Kinase | 2 |
| Creatinine | 1 |
| Gamma Glutamyl Transferase | 1 |
| Glucose | 1 |
| Lipase | 5 |
| Magnesium (Hyper) | 1 |
| Magnesium (Hypo) | 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).
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Pyrexia | 2 |
| Temperature intolerance | 1 |
| Hypertension | 3 |
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.
| Percentage of Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in Part 2 | 46.2 (26.6 to 66.6) | 61.5 (40.6 to 79.8) |
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.
| Percentage of Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Percentage of Participants With OR Per RECIST v1.1 in Part 1 | 71.4 (29.0 to 96.3) |
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.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| CR | 0 |
| PR | 5 |
| SD >=8 weeks | 2 |
| PD | 0 |
| NE | 0 |
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.
| Months | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Duration of Response (DoR) Per RECIST v1.1 in Part 1 | 6.0 (5.5 to NA) |
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.
| Percentage of Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Percentage of Participants With Disease Control (DC) Per RECIST v1.1 in Part 1 | 100 (59.0 to 100) |
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.
| Months | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Progression-Free Survival (PFS) Per RECIST v1.1 in Part 1 | 9.5 (7.8 to 18.2) |
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.
| Percentage of Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 1 | 28.6 (4.1 to 61.2) |
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.
| Months | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Overall Survival (OS) Per RECIST v1.1 in Part 1 | 30.1 (11.9 to NA) |
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.
| Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Any TEAE | 26 | 26 |
| Any TESAE | 7 | 12 |
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.
| Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Hemoglobin (Hypo) | 0 | 1 |
| Lymphocytes (Hyper) | 0 | 2 |
| Lymphocytes (Hypo) | 3 | 6 |
| Neutrophils | 7 | 8 |
| Platelets | 3 | 2 |
| Leukocytes (Hypo) | 2 | 4 |
| Activated Partial Thromboplastin Time | 5 | 5 |
| Albumin | 0 | 3 |
| Alkaline Phosphatase | 1 | 1 |
| Alanine Aminotransferase | 2 | 1 |
| Amylase | 7 | 3 |
| Aspartate Aminotransferase | 1 | 0 |
| Bilirubin | 1 | 1 |
| Calcium Corrected (Hypo) | 0 | 1 |
| Creatine Kinase | 2 | 3 |
| Creatinine | 2 | 2 |
| Gamma Glutamyl Transferase | 5 | 4 |
| Potassium (Hyper) | 0 | 2 |
| Potassium (Hypo) | 0 | 2 |
| Lipase | 12 | 15 |
| Magnesium (Hypo) | 0 | 1 |
| Sodium (Hypo) | 2 | 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).
| Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Pyrexia | 3 | 5 |
| Temperature intolerance | 5 | 5 |
| Hypertension | 4 | 4 |
| Hypotension | 1 | 1 |
| Supraventricular tachycardia | 1 | 0 |
| Ventricular tachycardia | 1 | 0 |
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.
| Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| CR | 0 | 1 |
| PR | 12 | 15 |
| SD >=8 weeks | 11 | 6 |
| PD | 1 | 3 |
| NE | 2 | 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. In Part 2, randomization occurred between Day -8 and the same date as dosing.
| Months | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| DoR Per RECIST v1.1 in Part 2 | 7.7 (4.6 to 15.4) | 10.3 (5.8 to NA) |
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.
| Percentage of Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Percentage of Participants With DC Per RECIST v1.1 in Part 2 | 88.5 (69.8 to 97.6) | 84.6 (65.1 to 95.6) |
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.
| Months | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| PFS Per RECIST v1.1 in Part 2 | 11.1 (7.3 to 16.2) | 10.9 (6.9 to 15.1) |
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.
| Percentage of Participants | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Percentage of Participants With PFS at 12 Months (PFS-12) Per RECIST v1.1 in Part 2 | 38.6 (18.6 to 58.3) | 36.1 (17.1 to 55.5) |
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.
| Months | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| OS Per RECIST v1.1 in Part 2 | NA (20.6 to NA) | 22.4 (10.6 to NA) |
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.
| ng/mL | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Cycle 1 Day 1 | NA ± NA | NA ± NA |
| Cycle 3 Day 1 | 67980 ± 20.31 | 48600 ± 39.67 |
| Cycle 7 Day 1 | 112500 ± 28.63 | 97610 ± 46.56 |
| Cycle 13 Day 1 | 101500 ± 30.22 | 147000 ± 30.57 |
| Cycle 27 Day 1 | — | 120700 ± 29.83 |
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.
| µg/mL | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| Cycle 1 Day 1 | NA ± NA | NA ± NA |
| Cycle 2 Day 1 | 111.2 ± 25.38 | 69.81 ± 199.1 |
| Cycle 7 Day 1 | 186.5 ± 53.45 | 159.8 ± 81.62 |
| Cycle 13 Day 1 | 146.7 ± 24.43 | 170.1 ± 35.77 |
| Cycle 27 Day 1 | — | 107.9 ± 30.42 |
Serum concentrations of bevacizumab collected over time in Part 1 (S1) are reported. The LLOQ for bevacizumab was considered to be 500 ng/mL.
| ng/mL | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| Cycle 1 Day 1 | NA ± NA |
| Cycle 2 Day 1 | 36090 ± 16.55 |
| Cycle 7 Day 1 | 73350 ± 39.94 |
| Cycle 13 Day 1 | 70370 ± 30.52 |
| Cycle 27 Day 1 | NA ± NA |
Number of participants with positive ADA to durvalumab in Part 1 (S1) and Part 2 (E1) are reported.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| ADA positive at baseline | 0 | 2 |
| ADA positive at Cycle 3 Day 1 | 0 | 1 |
| ADA positive at Cycle 7 Day 1 | 0 | 0 |
| ADA positive at Cycle 13 Day 1 | 0 | 0 |
| ADA positive at Cycle 27 Day 1 | — | 0 |
| ADA positive at 90 days post last dose | 0 | 0 |
Number of participants with positive ADA to oleclumab in Part 1 (S1) and Part 2 (E1) are reported.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|
| ADA positive at baseline | 0 | 0 |
| ADA positive at Cycle 2 Day 1 | 0 | 2 |
| ADA positive at Cycle 7 Day 1 | 0 | 0 |
| ADA positive at Cycle 13 Day 1 | 0 | 0 |
| ADA positive at Cycle 27 Day 1 | — | 0 |
| ADA positive at 90 days post last dose | 0 | 0 |
Number of participants with positive ADA to bevacizumab in Part 1 (S1) are reported.
| Participants | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|
| ADA positive at baseline | 0 |
| ADA positive at Cycle 2 Day 1 | 5 |
| ADA positive at Cycle 7 Day 1 | 7 |
| ADA positive at Cycle 13 Day 1 | 5 |
| ADA positive at Cycle 27 Day 1 | 1 |
| ADA positive at 90 days post last dose | 4 |
Collected over 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). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | 4/7 (57.1%) | 1/7 (14.3%) | 7/7 (100%) |
| Part 2 (C1): FOLFOX + Bevacizumab | 8/26 (30.8%) | 7/26 (26.9%) | 25/26 (96.2%) |
| Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | 13/26 (50%) | 12/26 (46.2%) | 26/26 (100%) |
| Event | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|---|
| ColitisGastrointestinal disorders | 1/7 | 0/26 | 0/26 |
| Large intestine perforationGastrointestinal disorders | 1/7 | 0/26 | 1/26 |
| Intestinal obstructionGastrointestinal disorders | 0/7 | 2/26 | 0/26 |
| Covid-19Infections and infestations | 0/7 | 1/26 | 2/26 |
| Ventricular tachycardiaCardiac disorders | 0/7 | 1/26 | 0/26 |
| Blood bilirubin increasedInvestigations | 0/7 | 0/26 | 1/26 |
| DehydrationMetabolism and nutrition disorders | 0/7 | 0/26 | 1/26 |
| BursitisMusculoskeletal and connective tissue disorders | 0/7 | 1/26 | 0/26 |
| Lumbar radiculopathyNervous system disorders | 0/7 | 0/26 | 1/26 |
| PyelocaliectasisRenal and urinary disorders | 0/7 | 0/26 | 1/26 |
| Event | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab |
|---|---|---|---|
| ParaesthesiaNervous system disorders | 5/7 | 7/26 | 5/26 |
| Peripheral sensory neuropathyNervous system disorders | 5/7 | 11/26 | 10/26 |
| DiarrhoeaGastrointestinal disorders | 5/7 | 12/26 | 14/26 |
| FatigueGeneral disorders | 5/7 | 10/26 | 11/26 |
| Neutrophil count decreasedInvestigations | 4/7 | 4/26 | 4/26 |
| NauseaGastrointestinal disorders | 2/7 | 13/26 | 12/26 |
| ConstipationGastrointestinal disorders | 3/7 | 9/26 | 12/26 |
| HypertensionVascular disorders | 3/7 | 4/26 | 4/26 |
| StomatitisGastrointestinal disorders | 3/7 | 5/26 | 8/26 |
| Decreased appetiteMetabolism and nutrition disorders | 1/7 | 5/26 | 8/26 |
As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Age, Continuous(Years) | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Total |
|---|---|---|---|---|
| Mean | 59.4 ± 12.4 | 55.5 ± 13.5 | 59.8 ± 12.5 | 57.9 ± 12.9 |
| Sex: Female, Male(Participants) | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Total |
|---|---|---|---|---|
| Female | 3 | 7 | 11 | 21 |
| Male | 4 | 19 | 15 | 38 |
| Ethnicity (NIH/OMB)(Participants) | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 4 | 1 | 5 |
| Not Hispanic or Latino | 7 | 19 | 23 | 49 |
| Unknown or Not Reported | 0 | 3 | 2 | 5 |
| Race (NIH/OMB)(Participants) | Part 1 (S1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Part 2 (C1): FOLFOX + Bevacizumab | Part 2 (E1): FOLFOX + Bevacizumab + Durvalumab + Oleclumab | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 0 | 1 |
| White | 7 | 20 | 23 | 50 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 4 | 1 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — 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.
Supporting information: Study protocol, Statistical analysis plan
Time frame: 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.
Access criteria: 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.
Data sharing details ↗ · astrazenecagroup-dt.pharmacm.com
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Studies of the drug tested here: Bevacizumab