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MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

Primary Purpose

Carcinoma, Metastatic Pancreatic Adenocarcinoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Oleclumab

Durvalumab

Gemcitabine

Nab-paclitaxel

Oxaliplatin

Folinic acid

5-FU

About this trial

This is an interventional treatment trial for Carcinoma focused on measuring MEDI9447, oleclumab, immunotherapy, pancreatic cancer, durvalumab

Eligibility Criteria

18 Years - 101 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18
Written and signed informed consent must be obtained
ECOG Performance Status 0 or 1
Weight ≥ 35 kg
Subjects must have histologically or cytologically, confirmed pancreatic adenocarcinoma:
Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1st line metastatic disease) not previously treated with systemic therapies.
Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2nd line metastatic disease
Subjects must have at least 1 measurable lesion according to RECIST v1.1
All subjects must consent to providing archival tumor specimens

Exclusion Criteria:

Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment.
Prior receipt of any immune-related therapy
Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
Subjects with a history of venous thrombosis within the past 3 months
Subjects with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment
Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
Other invasive malignancy within 2 years.
Any history of leptomeningeal disease or cord compression.
Current or prior use of immunosuppressive medication within 14 days prior to the first dose

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX

Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX

Dose-expansion, Gemcitabine + nab-paclitaxel

Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel

Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Arm Description

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-paclitaxel 125 mg/m^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

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 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

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 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

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 400 mg/m^2 IV bolus followed by 2400 mg/m^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

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, withdrawal of participant consent, or another discontinuation criterion is met.

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 repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Number of Participants With Overall Survival Events in Dose Expansion Phase

Overall Survival in Dose Expansion Phase

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.

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.

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.

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.

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.

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.

Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase

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.

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.

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.

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.

Serum Concentrations of Oleclumab

Serum concentrations of oleclumab are reported.

Serum Concentrations of Durvalumab

Serum concentrations of durvalumab are reported.

Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)

Plasma concentrations of gemcitabine and metabolite dFdU are reported.

Plasma Concentrations of Nab-paclitaxel

Plasma concentrations of nab-paclitaxel are reported.

Full Information

NCT ID

NCT03611556

First Posted

May 18, 2018

Last Updated

September 8, 2023

Sponsor

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT03611556

Brief Title

MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

Official Title

A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) With or Without Durvalumab in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

June 21, 2018 (Actual)

Primary Completion Date

July 22, 2022 (Actual)

Study Completion Date

July 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Metastatic Pancreatic Adenocarcinoma

Keywords

MEDI9447, oleclumab, immunotherapy, pancreatic cancer, durvalumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

213 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Arm Type

Experimental

Arm Description

Arm Title

Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Arm Type

Experimental

Arm Description

Arm Title

Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX

Arm Type

Experimental

Arm Description

Arm Title

Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX

Arm Type

Experimental

Arm Description

Arm Title

Dose-expansion, Gemcitabine + nab-paclitaxel

Arm Type

Active Comparator

Arm Description

Arm Title

Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel

Arm Type

Experimental

Arm Description

Arm Title

Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Oleclumab

Other Intervention Name(s)

MEDI9447

Intervention Description

Participants will receive IV infusion of oleclumab as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

Durvalumab

Other Intervention Name(s)

MEDI4736

Intervention Description

Participants will receive IV infusion of durvalumab as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Participants will receive IV infusion of gemcitabine as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

Nab-paclitaxel

Intervention Description

Participants will receive IV infusion of nab-paclitaxel as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

Modified FOLFOX (oxaliplatin, folinic acid, and 5-FU)

Intervention Description

Participants will receive IV infusion of oxaliplatin as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

Folinic acid

Other Intervention Name(s)

Modified FOLFOX (oxaliplatin, folinic acid, and 5-FU)

Intervention Description

Participants will receive IV infusion of folinic acid as stated in arm description.

Intervention Type

Drug

Intervention Name(s)

5-FU

Other Intervention Name(s)

Modified FOLFOX (oxaliplatin, folinic acid, and 5-FU)

Intervention Description

Participants will receive IV infusion of 5-FU as stated in arm description.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase

Description

Time Frame

Day 1 through 65.7 weeks (maximum observed duration)

Title

Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase

Description

Time Frame

From Day 1 to 28 days after the first dose of study drugs

Title

Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase

Description

Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.

Time Frame

Day 1 through 65.7 weeks (maximum observed duration)

Title

Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase

Description

Number of participants with abnormal ECG parameters reported as TEAEs are reported.

Time Frame

Day 1 through 65.7 weeks (maximum observed duration)

Title

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase

Description

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.

Time Frame

Day 1 through 65.7 weeks (maximum observed duration)

Title

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

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Secondary Outcome Measure Information:

Title

Number of Participants With TEAEs and TESAEs in Dose Expansion Phase

Description

Time Frame

Day 1 through 172.1 weeks (maximum observed duration)

Title

Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase

Description

Number of participants with abnormal vital signs (temperature, blood pressure, pulse rate, and respiratory rate) reported as TEAEs are reported.

Time Frame

Day 1 through 172.1 weeks (maximum observed duration)

Title

Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase

Description

Number of participants with abnormal ECG parameters reported as TEAEs are reported.

Time Frame

Day 1 through 172.1 weeks (maximum observed duration)

Title

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase

Description

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.

Time Frame

Day 1 through 172.1 weeks (maximum observed duration)

Title

Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase

Description

Time Frame

Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)

Title

Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase

Description

Time Frame

Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)

Title

Number of Participants With Overall Survival Events in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)

Title

Overall Survival in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)

Title

Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase

Description

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.

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)

Title

Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)

Title

Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

Description

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase

Description

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.

Time Frame

Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)

Title

Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab

Description

Time Frame

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)

Title

Number of Participants With Positive ADA to Durvalumab

Description

Time Frame

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)

Title

Serum Concentrations of Oleclumab

Description

Serum concentrations of oleclumab are reported.

Time Frame

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

Title

Serum Concentrations of Durvalumab

Description

Serum concentrations of durvalumab are reported.

Time Frame

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

Title

Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)

Description

Plasma concentrations of gemcitabine and metabolite dFdU are reported.

Time Frame

Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1

Title

Plasma Concentrations of Nab-paclitaxel

Description

Plasma concentrations of nab-paclitaxel are reported.

Time Frame

Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

101 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >= 18 Written and signed informed consent must be obtained Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Weight >= 35 kg Participants must have histologically or cytologically, confirmed pancreatic adenocarcinoma: Cohort A: Participants with previously untreated metastatic pancreatic adenocarcinoma (1L metastatic disease) not previously treated with systemic therapies Cohort B: Participants with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2L metastatic disease Participants must have at least 1 measurable lesion according to RECIST v1.1 All Participants must consent to providing archival tumor specimens. Exclusion Criteria: Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment. Prior receipt of any immune-related therapy Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed. Participants with a history of venous thrombosis within the past 3 months Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment Other invasive malignancy within 2 years Any history of leptomeningeal disease or cord compression Current or prior use of immunosuppressive medication within 14 days prior to the first dose.

Facility Information:

Facility Name

Research Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Research Site

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Research Site

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33901

Country

United States

Facility Name

Research Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Research Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Research Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Research Site

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

Research Site

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Research Site

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Research Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Facility Name

Research Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Research Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111

Country

United States

Facility Name

Research Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Research Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Research Site

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22908

Country

United States

Facility Name

Research Site

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

Research Site

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53705

Country

United States

Facility Name

Research Site

City

Blacktown

ZIP/Postal Code

2148

Country

Australia

Facility Name

Research Site

City

Clayton

ZIP/Postal Code

3168

Country

Australia

Facility Name

Research Site

City

Heidelberg

ZIP/Postal Code

3084

Country

Australia

Facility Name

Research Site

City

St Leonards

ZIP/Postal Code

2065

Country

Australia

Facility Name

Research Site

City

Oslo

ZIP/Postal Code

N-0379

Country

Norway

Facility Name

Research Site

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Research Site

City

Fuenlabrada

ZIP/Postal Code

28942

Country

Spain

Facility Name

Research Site

City

Oviedo

ZIP/Postal Code

33011

Country

Spain

Facility Name

Research Site

City

Pamplona

ZIP/Postal Code

31008

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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 Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing 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

IPD Sharing 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

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Links:

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D6070C00005&attachmentIdentifier=0fb0e4a6-ef94-4658-9a6d-b9d2f77f571f&fileName=d6070c00005-csp-amendment-3-Redacted.pdf&versionIdentifier=

Description

CSP redacted

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D6070C00005&attachmentIdentifier=636c01ef-f3da-4eec-b9de-de1fe3ac4864&fileName=d6070c00005-sap-ed-3-Redacted.pdf&versionIdentifier=

Description

SAP redacted

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D6070C00005&attachmentIdentifier=1f662c2d-1eb8-4c56-9b23-87d6bb71975d&fileName=d6070c00005-study-synopsis-Redacted-PDF-A.pdf&versionIdentifier=

Description

CSR Synopsis redacted

Learn more about this trial

MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

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MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

Carcinoma, Metastatic Pancreatic Adenocarcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial