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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 1
- 主要终点
- Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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-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.
干预措施: Nab-paclitaxel (Drug)
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 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.
干预措施: Oleclumab (Drug)
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-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.
干预措施: Oleclumab (Drug)
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-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.
干预措施: Durvalumab (Drug)
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-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.
干预措施: Gemcitabine (Drug)
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 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.
干预措施: Durvalumab (Drug)
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 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.
干预措施: Gemcitabine (Drug)
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 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.
干预措施: Nab-paclitaxel (Drug)
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 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.
干预措施: Oleclumab (Drug)
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 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.
干预措施: Durvalumab (Drug)
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 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.
干预措施: Oxaliplatin (Drug)
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 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.
干预措施: Folinic acid (Drug)
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 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.
干预措施: 5-FU (Drug)
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 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.
干预措施: Oleclumab (Drug)
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 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.
干预措施: Durvalumab (Drug)
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 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.
干预措施: Oxaliplatin (Drug)
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 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.
干预措施: Folinic acid (Drug)
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 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.
干预措施: 5-FU (Drug)
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, withdrawal of participant consent, or another discontinuation criterion is met.
干预措施: Gemcitabine (Drug)
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, withdrawal of participant consent, or another discontinuation criterion is met.
干预措施: Nab-paclitaxel (Drug)
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 repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.
干预措施: Oleclumab (Drug)
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 repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.
干预措施: Gemcitabine (Drug)
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 repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.
干预措施: Nab-paclitaxel (Drug)
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 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.
干预措施: Oleclumab (Drug)
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 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.
干预措施: Durvalumab (Drug)
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 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.
干预措施: Gemcitabine (Drug)
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 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.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase
时间窗: Day 1 through 65.7 weeks (maximum observed duration)
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
时间窗: Day 1 through 65.7 weeks (maximum observed duration)
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
时间窗: Day 1 through 65.7 weeks (maximum observed duration)
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase
时间窗: Day 1 through 65.7 weeks (maximum observed duration)
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.
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
时间窗: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
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.
Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase
时间窗: From Day 1 to 28 days after the first dose of study drugs
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.
次要结局
- Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase(Baseline (Days -28 to -1) through 36.1 months (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 Overall Survival Events in Dose Expansion Phase(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(Baseline (Days -28 to -1) through 36.1 months (maximum observed duration))
- Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab(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))
- Plasma Concentrations of Nab-paclitaxel(Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1)
- 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 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))
- Overall Survival in Dose Expansion Phase(Baseline (Days -28 to -1) through 38.7 months (maximum observed duration))
- Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase(Baseline (Days -28 to -1) through 36.1 months (maximum observed duration))
- Number of Participants With TEAEs and TESAEs in Dose Expansion Phase(Day 1 through 172.1 weeks (maximum observed duration))
- Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase(Baseline (Days -28 to -1) through 24.5 months (maximum observed duration))
- Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase(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(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(Baseline (Days -28 to -1) through 36.1 months (maximum observed duration))
- Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)(Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1)
- Number of Participants With Positive ADA to Durvalumab(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))
- Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase(Baseline (Days -28 to -1) through 38.7 months (maximum observed duration))
- Serum Concentrations of Durvalumab(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)
- Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase(Baseline (Days -28 to -1) through 38.7 months (maximum observed duration))
- Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase(Baseline (Days -28 to -1) through 36.1 months (maximum observed duration))
- Serum Concentrations of Oleclumab(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)