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2018-06-21
2022-07-22
2022-07-22
213
NCT03611556
MedImmune LLC
MedImmune LLC
INTERVENTIONAL
MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.
The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in participants with metastatic pancreatic cancer.
This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to assess the safety, preliminary antitumor activity, immunogenicity, and pharmacokinetics (PK) of oleclumab with or without durvalumab in combination with chemotherapy administered in participants with metastatic pancreatic ductal adenocarcinoma (PDAC). Participants with previously untreated metastatic PDAC (first-line [1L] metastatic PDAC) will be enrolled in Cohort A. Participants with metastatic PDAC previously treated with gemcitabine-based chemotherapy (without exposure to 5-fluorouracil [5-FU], capecitabine, or oxaliplatin; second-line [2L] metastatic PDAC) will be enrolled in Cohort B. The study consists of 2 parts, dose escalation (Part 1) and dose expansion (Part 2).
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2018-05-18 | 2023-07-20 | 2023-09-08 |
2018-07-26 | 2023-09-08 | 2023-10-03 |
2018-08-02 | 2023-10-03 | 2023-09 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Randomized
Interventional Model:
Parallel
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel Participants with 1L metastatic disease will receive intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclit | DRUG: Oleclumab
DRUG: Durvalumab
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
|
| EXPERIMENTAL: Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days | DRUG: Oleclumab
DRUG: Durvalumab
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
|
| EXPERIMENTAL: Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX Participants with 2L metastatic disease will receive IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU | DRUG: Oleclumab
DRUG: Durvalumab
DRUG: Oxaliplatin
DRUG: Folinic acid
DRUG: 5-FU
|
| EXPERIMENTAL: Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX Participants with 2L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m^2 IV; folinic acid 400 mg/m^2 IV; 5-FU | DRUG: Oxaliplatin
DRUG: Folinic acid
DRUG: 5-FU
|
| ACTIVE_COMPARATOR: Dose-expansion, Gemcitabine + nab-paclitaxel Participants with 1L metastatic disease will receive IV infusions of chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdr | DRUG: Gemcitabine
DRUG: Nab-paclitaxel
|
| EXPERIMENTAL: Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeat | |
| EXPERIMENTAL: Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2, both on Days |
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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 65.7 weeks (maximum observed duration) |
| Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | DLT: Any study drug related Grade (G)3 or higher toxicity including: any G4 immune-mediated AEs, >=G3 colitis/pneumonitis/interstitial lung disease (ILD), >=G3 nausea/vomiting/diarrhea that does not resolve to G2 or less within 3 days of maximal supportive care (MSC), G2 pneumonitis/ILD that does not resolve within 7 days of initiation of MSC, G4 anemia, G3 anemia with clinical sequelae/requires >2 units of red blood cells transfusion, G4 thrombocytopenia/neutropenia >=7 days, G3/4 thrombocytopenia with >=G3 hemorrhage, G4 febrile neutropenia (FN), G3 FN lasting >=5 days while receiving MSC, isolated G3 liver transaminase elevation (LTE)/ isolated G3 total bilirubin (TBL) that does not downgrade to G1 or less within 14 days of onset, isolated G4 LTE or TBL, elevated aspartate aminotransferase/alanine aminotransferase >3×upper limit of normal (ULN) and concurrent TBL >2×ULN without cholestasis or alternative explanations, any other toxicity judged as a DLT by Dose Escalation Committee. | From Day 1 to 28 days after the first dose of study drugs |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. | Day 1 through 65.7 weeks (maximum observed duration) |
| Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Number of participants with abnormal ECG parameters reported as TEAEs are reported. | Day 1 through 65.7 weeks (maximum observed duration) |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. | Day 1 through 65.7 weeks (maximum observed duration) |
| Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose Expansion Phase | The OR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions (TLs) and non-target lesions (NTLs), 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 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. Percentage of participants with OR is reported. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | Day 1 through 172.1 weeks (maximum observed duration) |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported. | Day 1 through 172.1 weeks (maximum observed duration) |
| Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Number of participants with abnormal ECG parameters reported as TEAEs are reported. | Day 1 through 172.1 weeks (maximum observed duration) |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. | Day 1 through 172.1 weeks (maximum observed duration) |
| Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase | The OR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, 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 sum of the diameters of target lesions (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 with OR is reported. | Baseline (Days -28 to -1) through 24.5 months (maximum observed duration) |
| Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase | The DC is defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is defined as disappearance of all TLs and NTLs, 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 date of first documentation. The SD is defined as neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for progressive disease (PD), taking as reference the smallest SoD while on study, and no new lesions. The PD is defined as at least a 20% increase in SoD of TLs, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. | Baseline (Days -28 to -1) through 24.5 months (maximum observed duration) |
| Number of Participants With Overall Survival Events in Dose Expansion Phase | The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. The number of participants with overall survival events (deaths) is reported. | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) |
| Overall Survival in Dose Expansion Phase | The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed using the Kaplan-Meier method. | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) |
| Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase | Progression-free survival (PFS) is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. The PD is defined as at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. The number of participants with PFS events is reported. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase | The PFS is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant received subsequent anticancer treatment prior to progression. The PD is defined as at least a 20% increase in sum of the diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of sum of the diameters, or unequivocal progression of existing non-target lesions, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment. The PFS is assessed using the Kaplan-Meier method. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase | The DoR is defined as the time from the first documentation of an OR until the first documentation of a PD or death due to any cause, whichever occurs first. The OR is defined as best overall response of confirmed CR or PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, 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. The PD is defined as at least a 20% increase in SoD of TLs, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. The DoR is assessed using the Kaplan-Meier method. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase | The DC is defined as confirmed CR, PR, or stable disease (SD) (maintained for >=8 weeks). The CR is defined as disappearance of all TLs and NTLs, 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 date of first documentation. The SD is defined as neither sufficient shrinkage of TLs to qualify for PR nor sufficient increase of TLs to qualify for PD, taking as reference the smallest SoD while on study, and no new lesions. The PD is defined as at least a 20% increase in SoD of TLs, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Percentage of participants with DC is reported. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | The OR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all TLs and NTLs, 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. The OR is assessed by cluster of differentiation 73 (CD73) expression level either low or high at baseline. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. The number of participants with overall survival events (deaths) is reported. | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) |
| Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | The overall survival is defined as the time from the randomization until death due to any cause. For participants who were alive at the time of data cut off, overall survival was censored on the last date when participants were known to be alive. The overall survival is assessed by CD73 expression level either low or high at baseline using the Kaplan-Meier method. The CD73 low is defined as no CD73 expression in tumor cells or <50% of tumor cells with 2+ or 3+ intensity and CD73 high is defined as CD73 expression with 2+ or 3+ intensity in >=50% of tumor cells. | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) |
| Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | PFS: Time from randomization until first documentation of PD/death due to any cause, whichever occurred first, regardless of whether participant received subsequent anticancer treatment prior to progression. PD:>=20% increase in SoD of TLs and an absolute increase of >= 5 mm of SoD/unequivocal progression of existing NTLs/appearance of new lesion. Participants who had no documented progression and were still alive at the time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. Number of participants with PFS events is reported. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | The PFS is defined as the time from randomization until the first documentation of a PD or death due to any cause, whichever occurred first, regardless of whether the participant receives subsequent anticancer treatment prior to progression. The PD is defined as at least a 20% increase in SoD of TLs, taking as reference the smallest sum on study and an absolute increase of at least 5 mm of SoD, or unequivocal progression of existing NTLs, or the appearance of new lesion/s. Participants who had no documented progression and were still alive at time of analysis were censored at time of latest date of assessment from their last evaluable RECIST v1.1 assessment. PFS is assessed by CD73 expression level either low/high at baseline using Kaplan-Meier method. CD73 low: No CD73 expression in tumor cells/<50% of tumor cells with 2+/3+ intensity. CD73 high: CD73 expression with 2+/3+ intensity in >=50% of tumor cells. | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Number of participants with positive ADA to oleclumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. | Day 1 through 172.1 weeks (Pre-dose on Cycle [C] 1 Day [D] 1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of oleclumab) |
| Number of Participants With Positive ADA to Durvalumab | Number of participants with positive ADA to durvalumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments (with <16 weeks between first and last positive). Treatment-boosted ADA is defined as baseline ADA positive titer that was boosted to a 4-fold or higher level following drug administration. | Day 1 through 128 weeks (Pre-dose on C1D1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of durvalumab) |
| Serum Concentrations of Oleclumab | Serum concentrations of oleclumab are reported. | Ten minutes (mins) (± 5 mins) post end of infusion (EOI), approximately 1 hour (+ 15 mins) after start of infusion on C1D1, C3D1, and C5D1; and pre-dose on C3D1 and C5D1 |
| Serum Concentrations of Durvalumab | Serum concentrations of durvalumab are reported. | Ten mins (± 5 mins) post EOI, approximately 1 hour (+ 15 mins) after start of infusion on C1D1 and C5D1; and pre-dose on C2D1 and C5D1 |
| Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Plasma concentrations of gemcitabine and metabolite dFdU are reported. | Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1 |
| Plasma Concentrations of Nab-paclitaxel | Plasma concentrations of nab-paclitaxel are reported. | Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1 |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
