MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.
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
2 other identifiers
interventional
213
4 countries
27
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2018
Longer than P75 for phase_1
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 18, 2018
CompletedStudy Start
First participant enrolled
June 21, 2018
CompletedFirst Posted
Study publicly available on registry
August 2, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 22, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 22, 2022
CompletedResults Posted
Study results publicly available
October 3, 2023
CompletedOctober 3, 2023
September 1, 2023
4.1 years
May 18, 2018
July 20, 2023
September 8, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
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 \>3Ă—upper limit of normal (ULN) and concurrent TBL \>2Ă—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 Outcomes (23)
Number of Participants With TEAEs and TESAEs in Dose Expansion Phase
Day 1 through 172.1 weeks (maximum observed duration)
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase
Day 1 through 172.1 weeks (maximum observed duration)
Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase
Day 1 through 172.1 weeks (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase
Day 1 through 172.1 weeks (maximum observed duration)
Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase
Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
- +18 more secondary outcomes
Study Arms (7)
Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel
EXPERIMENTALParticipants 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.
Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel
EXPERIMENTALParticipants 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.
Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX
EXPERIMENTALParticipants 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.
Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX
EXPERIMENTALParticipants 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.
Dose-expansion, Gemcitabine + nab-paclitaxel
ACTIVE COMPARATORParticipants 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.
Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel
EXPERIMENTALParticipants 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.
Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel
EXPERIMENTALParticipants 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.
Interventions
Participants will receive IV infusion of oleclumab as stated in arm description.
Participants will receive IV infusion of durvalumab as stated in arm description.
Participants will receive IV infusion of gemcitabine as stated in arm description.
Participants will receive IV infusion of nab-paclitaxel as stated in arm description.
Participants will receive IV infusion of oxaliplatin as stated in arm description.
Participants will receive IV infusion of folinic acid as stated in arm description.
Participants will receive IV infusion of 5-FU as stated in arm description.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedImmune LLClead
Study Sites (27)
Research Site
La Jolla, California, 92093, United States
Research Site
Aurora, Colorado, 80045, United States
Research Site
Fort Myers, Florida, 33901, United States
Research Site
Atlanta, Georgia, 30322, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
Ann Arbor, Michigan, 48109, United States
Research Site
Buffalo, New York, 14263, United States
Research Site
Durham, North Carolina, 27710, United States
Research Site
Cincinnati, Ohio, 45219, United States
Research Site
Columbus, Ohio, 43210, United States
Research Site
Philadelphia, Pennsylvania, 19111, United States
Research Site
Nashville, Tennessee, 37203, United States
Research Site
Dallas, Texas, 75235, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Charlottesville, Virginia, 22908, United States
Research Site
Seattle, Washington, 98109, United States
Research Site
Madison, Wisconsin, 53705, United States
Research Site
Blacktown, 2148, Australia
Research Site
Clayton, 3168, Australia
Research Site
Heidelberg, 3084, Australia
Research Site
St Leonards, 2065, Australia
Research Site
Oslo, N-0379, Norway
Research Site
Barcelona, 08035, Spain
Research Site
Fuenlabrada, 28942, Spain
Research Site
Oviedo, 33011, Spain
Research Site
Pamplona, 31008, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Dose escalation phase: Participants not enrolled in oleclumab 750 mg cohort. Dose expansion phase: Outcomes of mFOLFOX cohorts not included as enrollment was not opened. Non-compartmental PK data analysis were planned to be performed from each dose cohort if data allowed, but as sparse PK samples were collected, no non-compartmental PK parameters were calculated. Consequently, PK concentration time data only have been reported.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical study Information Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 18, 2018
First Posted
August 2, 2018
Study Start
June 21, 2018
Primary Completion
July 22, 2022
Study Completion
July 22, 2022
Last Updated
October 3, 2023
Results First Posted
October 3, 2023
Record last verified: 2023-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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
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.