Carcinoma, Metastatic Pancreatic Adenocarcinoma
Conditions
Keywords
MEDI9447, oleclumab, immunotherapy, pancreatic cancer, durvalumab
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).
Interventions
DRUGOleclumab
Participants will receive IV infusion of oleclumab as stated in arm description.
DRUGDurvalumab
Participants will receive IV infusion of durvalumab as stated in arm description.
DRUGGemcitabine
Participants will receive IV infusion of gemcitabine as stated in arm description.
DRUGNab-paclitaxel
Participants will receive IV infusion of nab-paclitaxel as stated in arm description.
DRUGOxaliplatin
Participants will receive IV infusion of oxaliplatin as stated in arm description.
DRUGFolinic acid
Participants will receive IV infusion of folinic acid as stated in arm description.
DRUG5-FU
Participants will receive IV infusion of 5-FU as stated in arm description.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
1. Age \>= 18 2. Written and signed informed consent must be obtained 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 4. Weight \>= 35 kg 5. 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 6. Participants must have at least 1 measurable lesion according to RECIST v1.1 7. All Participants must consent to providing archival tumor specimens.
Exclusion criteria
1. 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. 2. Prior receipt of any immune-related therapy 3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed. 4. Participants with a history of venous thrombosis within the past 3 months 5. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment 6. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment 7. Other invasive malignancy within 2 years 8. Any history of leptomeningeal disease or cord compression 9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | 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. |
| Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | 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. |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | 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 | 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 | Day 1 through 65.7 weeks (maximum observed duration) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival Events in Dose Expansion Phase | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) | 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. |
| Overall Survival in Dose Expansion Phase | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) | 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. |
| 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) | 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 | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) | 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. |
| Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Day 1 through 172.1 weeks (maximum observed duration) | 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 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) | 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 | Baseline (Days -28 to -1) through 36.1 months (maximum observed duration) | 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 | 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 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 | 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 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 | 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 oleclumab are reported. |
| 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 | Serum concentrations of durvalumab are reported. |
| 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 | Plasma concentrations of gemcitabine and metabolite dFdU are reported. |
| 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 | Plasma concentrations of nab-paclitaxel are reported. |
| Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | Baseline (Days -28 to -1) through 38.7 months (maximum observed duration) | 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. |
| 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 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 | Day 1 through 172.1 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 Expansion Phase | Day 1 through 172.1 weeks (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 24.5 months (maximum observed duration) | 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 | Baseline (Days -28 to -1) through 24.5 months (maximum observed duration) | 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. |
Countries
Australia, Norway, Spain, United States
Participant flow
Pre-assignment details
A total of 25 participants were treated in dose escalation part of this study. A total of 188 participants were randomised in dose expansion part of this study of which 170 participants were treated (18 participants were randomised but not treated). Results are presented for 195 treated participants only.
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel Participants with 1L metastatic disease received IV infusions of oleclumab 1500 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 was met. | 7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel Participants with 1L metastatic disease received 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 was met. | 7 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX Participants with second-line (2L) metastatic disease received 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; fluorouracil \[5-FU\] 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 was met. | 3 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX Participants with 2L metastatic disease received 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 was met. | 8 |
| Dose-expansion, Gemcitabine + Nab-paclitaxel Participants with 1L metastatic disease received 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 was met. | 62 |
| Dose-expansion, Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel Participants with 1L metastatic disease received 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 was met. | 38 |
| Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel Participants with 1L metastatic disease received 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 was met. | 70 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 7 | 7 | 3 | 8 | 47 | 32 | 53 |
| Overall Study | Reasons | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
| Overall Study | Sponsor decision | 0 | 0 | 0 | 0 | 9 | 4 | 12 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 4 | 2 | 4 |
Baseline characteristics
| Characteristic | 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 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 12.8 | 59.6 Years STANDARD_DEVIATION 11.4 | 67.0 Years STANDARD_DEVIATION 14.9 | 64.8 Years STANDARD_DEVIATION 4.8 | 65.6 Years STANDARD_DEVIATION 8 | 62.5 Years STANDARD_DEVIATION 11.1 | 62.9 Years STANDARD_DEVIATION 8.3 | 63.8 Years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 3 Participants | 7 Participants | 61 Participants | 37 Participants | 69 Participants | 191 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 3 Participants | 6 Participants | 54 Participants | 33 Participants | 64 Participants | 171 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants | 4 Participants | 26 Participants | 17 Participants | 34 Participants | 89 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 36 Participants | 21 Participants | 36 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 7 | 7 / 7 | 3 / 3 | 8 / 8 | 47 / 62 | 32 / 38 | 53 / 70 |
| other Total, other adverse events | 7 / 7 | 7 / 7 | 3 / 3 | 8 / 8 | 60 / 62 | 36 / 38 | 70 / 70 |
| serious Total, serious adverse events | 4 / 7 | 6 / 7 | 0 / 3 | 4 / 8 | 34 / 62 | 24 / 38 | 37 / 70 |
Outcome results
Primary
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.
Time frame: Day 1 through 65.7 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Platelet count decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutrophil count decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lymphocyte count decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood bilirubin increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Amylase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | International normalised ratio increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood glucose decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood creatinine increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyperthyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Thrombocytopenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lipase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Proteinuria | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypophosphataemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypothyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Gamma-glutamyltransferase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyponatraemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypomagnesaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Alanine aminotransferase increased | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutropenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypokalaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypocalcaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Aspartate aminotransferase increased | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Anaemia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypoalbuminaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | White blood cell count decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood alkaline phosphatase increased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood alkaline phosphatase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Anaemia | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutropenia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Thrombocytopenia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypothyroidism | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Alanine aminotransferase increased | 4 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Aspartate aminotransferase increased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood bilirubin increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood creatinine increased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood glucose decreased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | International normalised ratio increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lymphocyte count decreased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutrophil count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Platelet count decreased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | White blood cell count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypoalbuminaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypocalcaemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypokalaemia | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypomagnesaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyponatraemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypophosphataemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Proteinuria | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyperthyroidism | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Amylase increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Gamma-glutamyltransferase increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lipase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | White blood cell count decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyponatraemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Anaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypocalcaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lipase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypophosphataemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Platelet count decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Thrombocytopenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Gamma-glutamyltransferase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood creatinine increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Alanine aminotransferase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Amylase increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Proteinuria | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood glucose decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypokalaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood bilirubin increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Aspartate aminotransferase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | International normalised ratio increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutropenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypoalbuminaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypomagnesaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lymphocyte count decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyperthyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood alkaline phosphatase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypothyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutrophil count decreased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypophosphataemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lipase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Platelet count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Aspartate aminotransferase increased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyperthyroidism | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | White blood cell count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypoalbuminaemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Alanine aminotransferase increased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypocalcaemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypokalaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypothyroidism | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Amylase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hypomagnesaemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Anaemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Hyponatraemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Thrombocytopenia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutrophil count decreased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood creatinine increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood bilirubin increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood glucose decreased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Proteinuria | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | International normalised ratio increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Blood alkaline phosphatase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Neutropenia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Lymphocyte count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase | Gamma-glutamyltransferase increased | 1 Participants |
Primary
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.
Time frame: Day 1 through 65.7 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrial fibrillation | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrioventricular block | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Tachycardia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrial fibrillation | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrioventricular block | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Tachycardia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Tachycardia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrial fibrillation | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrioventricular block | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrial fibrillation | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Atrioventricular block | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase | Tachycardia | 0 Participants |
Primary
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.
Time frame: Day 1 through 65.7 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Pyrexia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypotension | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea exertional | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypertension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Temperature intolerance | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea exertional | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Pyrexia | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypotension | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Temperature intolerance | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypertension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypotension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypertension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Temperature intolerance | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Pyrexia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea exertional | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypertension | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Temperature intolerance | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Hypotension | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Pyrexia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase | Dyspnoea exertional | 0 Participants |
Primary
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.
Time frame: From Day 1 to 28 days after the first dose of study drugs
Population: The DLT-evaluable population included all participants enrolled in the dose-escalation phase who received all planned doses of study drugs during the DLT evaluation period and completed the safety follow-up through the DLT evaluation period or experienced any DLT during the DLT-evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase | 1 Participants |
Primary
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.
Time frame: Day 1 through 65.7 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TEAEs | 7 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TESAEs | 4 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TESAEs | 6 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TEAEs | 7 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TEAEs | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TESAEs | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TEAEs | 8 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase | Any TESAEs | 4 Participants |
Primary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The intent-to treat (ITT) population included all participants who were randomized and received any study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 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 | 29.0 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | 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 | 21.1 Percentage of Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | 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 | 32.9 Percentage of Participants |
p-value: 0.361495% CI: [-27.6, 12.1]Cochran-Mantel-Haenszel
p-value: 0.650395% CI: [-13.2, 20.7]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. The DoR is assessed for only those participants who had OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase | 7.2 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase | 12.9 Months |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase | 9.5 Months |
Secondary
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.
Time frame: Day 1 through 172.1 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutropenia | 22 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood alkaline phosphatase increased | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypokalaemia | 4 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Febrile neutropenia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood bilirubin increased | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperkalaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypomagnesaemia | 4 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood creatinine increased | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytopenia | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood glucose increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase increased | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyponatraemia | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood lactate dehydrogenase increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoalbuminaemia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukocytosis | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood magnesium decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Aspartate aminotransferase increased | 11 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytosis | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood oestrogen decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypophosphataemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count decreased | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Gamma-glutamyltransferase increased | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Troponin I increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypovolaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Haemoglobin decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypocalcaemia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperthyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | International normalised ratio increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperglycaemia | 4 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Iron deficiency | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lipase increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphopenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Anaemia | 17 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Liver function test increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood albumin decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypothyroidism | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphocyte count decreased | 4 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Type 2 diabetes mellitus | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoglycaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukopenia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count decreased | 19 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Proteinuria | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypertransaminasaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Platelet count decreased | 13 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Amylase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Platelet count decreased | 9 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Troponin I increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukopenia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count decreased | 6 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase decreased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperglycaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperkalaemia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoalbuminaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase increased | 9 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypocalcaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoglycaemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypokalaemia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Amylase increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypomagnesaemia | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphopenia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyponatraemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypophosphataemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Aspartate aminotransferase increased | 8 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypovolaemia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Febrile neutropenia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Iron deficiency | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Type 2 diabetes mellitus | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood albumin decreased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Proteinuria | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood alkaline phosphatase increased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutropenia | 15 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood bilirubin increased | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Anaemia | 14 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood creatinine increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood glucose increased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytopenia | 7 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood lactate dehydrogenase increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood magnesium decreased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood oestrogen decreased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytosis | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Gamma-glutamyltransferase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukocytosis | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Haemoglobin decreased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | International normalised ratio increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperthyroidism | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lipase increased | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Liver function test increased | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphocyte count decreased | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypothyroidism | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count decreased | 8 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypertransaminasaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Anaemia | 28 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Febrile neutropenia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukocytosis | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Leukopenia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphopenia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutropenia | 16 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytopenia | 13 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Thrombocytosis | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperthyroidism | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypothyroidism | 7 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypertransaminasaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Alanine aminotransferase increased | 16 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Amylase increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Aspartate aminotransferase increased | 15 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood albumin decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood alkaline phosphatase increased | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood bilirubin increased | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood creatinine increased | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood glucose increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood lactate dehydrogenase increased | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood magnesium decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Blood oestrogen decreased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Gamma-glutamyltransferase increased | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Haemoglobin decreased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | International normalised ratio increased | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lipase increased | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Liver function test increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Lymphocyte count decreased | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Proteinuria | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Neutrophil count decreased | 24 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Platelet count decreased | 20 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Troponin I increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count decreased | 10 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | White blood cell count increased | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperglycaemia | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyperkalaemia | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoalbuminaemia | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypocalcaemia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypoglycaemia | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypokalaemia | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypomagnesaemia | 6 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hyponatraemia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypophosphataemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Hypovolaemia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Iron deficiency | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase | Type 2 diabetes mellitus | 0 Participants |
Secondary
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.
Time frame: Day 1 through 172.1 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Supraventricular tachycardia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Tachycardia | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Supraventricular tachycardia | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Tachycardia | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Supraventricular tachycardia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase | Tachycardia | 3 Participants |
Secondary
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.
Time frame: Day 1 through 172.1 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Pyrexia | 15 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypertension | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea exertional | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypothermia | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Orthostatic hypotension | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypotension | 3 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea | 7 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea exertional | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypothermia | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Pyrexia | 12 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea | 6 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypertension | 3 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypotension | 4 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Orthostatic hypotension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypertension | 11 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Pyrexia | 21 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Orthostatic hypotension | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypotension | 4 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea exertional | 2 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Dyspnoea | 8 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase | Hypothermia | 1 Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, number of participants analyzed (N) signified those participants who had high or low levels of CD73.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 37 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 22 Participants with event |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 39 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 10 Participants with event |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 10 Participants with event |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase | 14 Participants with event |
95% CI: [0.676, 1.985]
95% CI: [0.377, 0.968]
95% CI: [0.622, 3.917]
95% CI: [0.638, 3.576]
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Overall Survival Events in Dose Expansion Phase | 47 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Overall Survival Events in Dose Expansion Phase | 32 Participants with event |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Overall Survival Events in Dose Expansion Phase | 53 Participants with event |
95% CI: [0.79, 1.983]
95% CI: [0.498, 1.131]
Secondary
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.
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)
Population: The ADA evaluable durvalumab population included all participants who received durvalumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | ADA positive post-baseline | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Persistent Positive | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Persistent Positive | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | ADA positive post-baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive ADA to Durvalumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Persistent Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | ADA positive post-baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | Persistent Positive | 2 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive ADA to Durvalumab | ADA positive post-baseline | 2 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive ADA to Durvalumab | Persistent Positive | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive ADA to Durvalumab | Transient Positive | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive ADA to Durvalumab | ADA positive at baseline | 2 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive ADA to Durvalumab | Treatment-boosted ADA | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive ADA to Durvalumab | ADA positive post-baseline | 0 Participants |
Secondary
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.
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)
Population: The ADA evaluable oleclumab population included all participants who received oleclumab, analyzed according to the treatment they actually received, and who had a non-missing baseline ADA result and at least one non-missing post-baseline ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 1 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 1 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 1 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 0 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 1 Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Treatment-boosted ADA | 0 Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive at baseline | 0 Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | ADA positive post-baseline | 0 Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Transient Positive | 0 Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab | Persistent Positive | 0 Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, number of participants analyzed (N) signified those participants who had high or low levels of CD73.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 35 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 23 Participants with event |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 39 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 8 Participants with event |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 9 Participants with event |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 12 Participants with event |
95% CI: [0.584, 1.693]
95% CI: [0.366, 0.973]
95% CI: [0.716, 5.437]
95% CI: [0.55, 3.707]
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase | 43 Participants with event |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase | 32 Participants with event |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase | 51 Participants with event |
95% CI: [0.726, 1.837]
95% CI: [0.468, 1.105]
Secondary
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.
Time frame: Day 1 through 172.1 weeks (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TEAEs | 62 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TESAEs | 34 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TEAEs | 37 Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TESAEs | 24 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TEAEs | 70 Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Number of Participants With TEAEs and TESAEs in Dose Expansion Phase | Any TESAEs | 37 Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, number of participants analyzed (N) signified those participants who had high or low levels of CD73.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 9.9 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 7.9 Months |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 12.1 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 22.2 Months |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 16.0 Months |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase | 16.1 Months |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Overall Survival in Dose Expansion Phase | 10.8 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Overall Survival in Dose Expansion Phase | 8.9 Months |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Overall Survival in Dose Expansion Phase | 12.9 Months |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase | 66.1 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase | 73.7 Percentage of Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase | 75.7 Percentage of Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase | 42.9 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase | 71.4 Percentage of Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase | 66.7 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase | 62.5 Percentage of Participants |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, number of participants analyzed (N) signified those participants who had high or low levels of CD73.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 23.9 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 22.2 Percentage of Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 31.4 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 43.8 Percentage of Participants |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 18.2 Percentage of Participants |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 36.8 Percentage of Participants |
95% CI: [-25.2, 21.9]
95% CI: [-12.6, 27]
95% CI: [-58.3, 13.9]
95% CI: [-39.1, 26.6]
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
Population: As-treated population included all participants who received any study drugs and were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase | 0 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase | 14.3 Percentage of Participants |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase | 0 Percentage of Participants |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase | 12.5 Percentage of Participants |
Secondary
Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)
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
Population: The PK evaluable gemcitabine population included all participants who received at least one dose of gemcitabine and who had at least one reportable PK concentration. Here, number analyzed (n) denotes those participants who were analyzed for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C1D1 (EOI) | 3194 ng/mL | Geometric Coefficient of Variation 64.74 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (EOI) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C1D1 (EOI) | 33700 ng/mL | Geometric Coefficient of Variation 14.7 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (EOI) | NA ng/mL | — |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (pre-dose) | 434.6 ng/mL | Geometric Coefficient of Variation 344.7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (EOI) | 34550 ng/mL | Geometric Coefficient of Variation 35.37 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C1D1 (EOI) | 4659 ng/mL | Geometric Coefficient of Variation 67.41 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (EOI) | 3530 ng/mL | Geometric Coefficient of Variation 48.11 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C1D1 (EOI) | 32160 ng/mL | Geometric Coefficient of Variation 17.67 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C1D1 (EOI) | 29510 ng/mL | Geometric Coefficient of Variation 113.4 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (pre-dose) | 245.1 ng/mL | Geometric Coefficient of Variation 361.5 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C1D1 (EOI) | 3301 ng/mL | Geometric Coefficient of Variation 192 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (EOI) | 1748 ng/mL | Geometric Coefficient of Variation 236.5 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (EOI) | 23900 ng/mL | Geometric Coefficient of Variation 189.1 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C1D1 (EOI) | 32350 ng/mL | Geometric Coefficient of Variation 17.1 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (EOI) | 1431 ng/mL | Geometric Coefficient of Variation 446.3 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (EOI) | 21970 ng/mL | Geometric Coefficient of Variation 130.3 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (pre-dose) | 149.9 ng/mL | Geometric Coefficient of Variation 147 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C1D1 (EOI) | 3315 ng/mL | Geometric Coefficient of Variation 135.4 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (pre-dose) | 177.5 ng/mL | Geometric Coefficient of Variation 170 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (EOI) | 2998 ng/mL | Geometric Coefficient of Variation 151.3 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C4D1 (pre-dose) | NA ng/mL | — |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C4D1 (EOI) | 27260 ng/mL | Geometric Coefficient of Variation 43.07 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | dFdU C1D1 (EOI) | 26300 ng/mL | Geometric Coefficient of Variation 163.9 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU) | Gemcitabine C1D1 (EOI) | 4086 ng/mL | Geometric Coefficient of Variation 148.9 |
Secondary
Plasma Concentrations of Nab-paclitaxel
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
Population: The PK evaluable nab-paclitaxel population included all participants who received at least one dose of nab-paclitaxel and who had at least one reportable PK concentration. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples. Here, number analyzed (n) denotes those participants who were analyzed for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C1D1 (EOI) | 1711 ng/mL | Geometric Coefficient of Variation 80.37 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C4D1 (EOI) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C1D1 (EOI) | 2685 ng/mL | Geometric Coefficient of Variation 63.55 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Plasma Concentrations of Nab-paclitaxel | C4D1 (EOI) | 1474 ng/mL | Geometric Coefficient of Variation 96.12 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C4D1 (pre-dose) | NA ng/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C1D1 (EOI) | 2381 ng/mL | Geometric Coefficient of Variation 105.2 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C4D1 (EOI) | 1825 ng/mL | Geometric Coefficient of Variation 178.1 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C1D1 (EOI) | 2711 ng/mL | Geometric Coefficient of Variation 81.67 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C4D1 (EOI) | 1445 ng/mL | Geometric Coefficient of Variation 145.8 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Plasma Concentrations of Nab-paclitaxel | C4D1 (pre-dose) | NA ng/mL | — |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Nab-paclitaxel | C4D1 (pre-dose) | NA ng/mL | — |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Nab-paclitaxel | C1D1 (EOI) | 2611 ng/mL | Geometric Coefficient of Variation 142 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Plasma Concentrations of Nab-paclitaxel | C4D1 (EOI) | 1747 ng/mL | Geometric Coefficient of Variation 99.26 |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment. Here, number of participants analyzed (N) signified those participants who had high or low levels of CD73.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 5.6 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 5.2 Months |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 5.5 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 10.5 Months |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 7.6 Months |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase | 10.9 Months |
Secondary
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.
Time frame: Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Population: The ITT population included all participants who were randomized and received any amount of study drugs and were analyzed according to randomized treatment assignment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase | 6.7 Months |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase | 5.6 Months |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase | 7.5 Months |
Secondary
Serum Concentrations of Durvalumab
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
Population: The PK evaluable durvalumab population included all participants who received at least one dose of durvalumab and who had at least one reportable PK concentration. Here, number of participants analyzed (N) indicates those participants who had adequate PK samples. Here, number analyzed (n) denotes those participants who were analyzed for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C1D1 (EOI) | 292.5 μg/mL | Geometric Coefficient of Variation 11.72 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C5D1 (pre-dose) | NA μg/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C2D1 (pre-dose) | 35.97 μg/mL | Geometric Coefficient of Variation 51.44 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C5D1 (EOI) | NA μg/mL | — |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C1D1 (EOI) | 374.5 μg/mL | Geometric Coefficient of Variation 27.5 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C5D1 (pre-dose) | 74.52 μg/mL | Geometric Coefficient of Variation 28.32 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C5D1 (EOI) | 522.1 μg/mL | Geometric Coefficient of Variation 46.72 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Durvalumab | C2D1 (pre-dose) | 14.39 μg/mL | Geometric Coefficient of Variation 5129 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C2D1 (pre-dose) | 50.52 μg/mL | Geometric Coefficient of Variation 57.3 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C1D1 (EOI) | 309.0 μg/mL | Geometric Coefficient of Variation 11.58 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C5D1 (EOI) | 664.5 μg/mL | Geometric Coefficient of Variation 28.14 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C1D1 (EOI) | 380.7 μg/mL | Geometric Coefficient of Variation 56.89 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C2D1 (pre-dose) | 59.97 μg/mL | Geometric Coefficient of Variation 176.7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Durvalumab | C5D1 (pre-dose) | 175.9 μg/mL | Geometric Coefficient of Variation 43.5 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Durvalumab | C5D1 (pre-dose) | 137.9 μg/mL | Geometric Coefficient of Variation 48.85 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Durvalumab | C2D1 (pre-dose) | 86.20 μg/mL | Geometric Coefficient of Variation 97.95 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Durvalumab | C1D1 (EOI) | 345.8 μg/mL | Geometric Coefficient of Variation 324.2 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Durvalumab | C5D1 (EOI) | 597.9 μg/mL | Geometric Coefficient of Variation 23.4 |
Secondary
Serum Concentrations of Oleclumab
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
Population: Pharmacokinetic (PK) evaluable oleclumab population included all participants who received at least one dose of oleclumab and who had at least one reportable PK concentration. Here, number analyzed (n) denotes those participants who were analyzed for the specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C5D1 (pre-dose) | NA μg/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C5D1 (EOI) | NA μg/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 128.6 μg/mL | Geometric Coefficient of Variation 10 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C3D1 (EOI) | NA μg/mL | — |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C1D1 (EOI) | 297.6 μg/mL | Geometric Coefficient of Variation 25.7 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C3D1 (EOI) | 870.3 μg/mL | Geometric Coefficient of Variation 21.86 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C5D1 (pre-dose) | 73.19 μg/mL | Geometric Coefficient of Variation 130.2 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C1D1 (EOI) | 710.2 μg/mL | Geometric Coefficient of Variation 21.42 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C5D1 (EOI) | 948.3 μg/mL | Geometric Coefficient of Variation 44.9 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 211.5 μg/mL | Geometric Coefficient of Variation 73.4 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C1D1 (EOI) | 412.7 μg/mL | Geometric Coefficient of Variation 11.12 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 134.3 μg/mL | Geometric Coefficient of Variation 141.5 |
| Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C3D1 (EOI) | 571.1 μg/mL | Geometric Coefficient of Variation 15.75 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C3D1 (EOI) | 1181 μg/mL | Geometric Coefficient of Variation 24.97 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C1D1 (EOI) | 734.6 μg/mL | Geometric Coefficient of Variation 41.01 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C5D1 (EOI) | 1057 μg/mL | Geometric Coefficient of Variation 14.88 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C5D1 (pre-dose) | 235.7 μg/mL | Geometric Coefficient of Variation 27.68 |
| Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 368.9 μg/mL | Geometric Coefficient of Variation 2.461 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 164.8 μg/mL | Geometric Coefficient of Variation 324.1 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C3D1 (EOI) | 893.0 μg/mL | Geometric Coefficient of Variation 30.66 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C1D1 (EOI) | 704.4 μg/mL | Geometric Coefficient of Variation 30.28 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C5D1 (pre-dose) | 85.99 μg/mL | Geometric Coefficient of Variation 192 |
| Oleclumab 3000 mg + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C5D1 (EOI) | 852.8 μg/mL | Geometric Coefficient of Variation 24.77 |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C3D1 (pre-dose) | 226.8 μg/mL | Geometric Coefficient of Variation 70.41 |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C1D1 (EOI) | 725.9 μg/mL | Geometric Coefficient of Variation 34.69 |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C3D1 (EOI) | 894.4 μg/mL | Geometric Coefficient of Variation 39.22 |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C5D1 (EOI) | 753.2 μg/mL | Geometric Coefficient of Variation 41.32 |
| Oleclumab 3000 mg + Durvalumab + Gemcitabine + Nab-paclitaxel: CD73 Level = Low | Serum Concentrations of Oleclumab | C5D1 (pre-dose) | 116.4 μg/mL | Geometric Coefficient of Variation 54 |