Locally Advanced or Metastatic Solid Tumours
Conditions
Keywords
AZD0171, Durvalumab, Gemcitabine, Nab-paclitaxel, Leukaemia inhibitory factor, Pancreatic ductal adenocarcinoma, Immunotherapy
Brief summary
The proposed study is designed to examine the effects of AZD0171 and durvalumab in combination with standard-of-care chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).
Detailed description
This is a Phase II, open-label, single arm, multicentre study to assess the safety, preliminary antitumour activity, immunogenicity, pharmacodynamics (PD), and pharmacokinetics (PK) of AZD0171 in combination with durvalumab and standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) in participants with first line (1L) metastatic pancreatic ductal adenocarcinoma (mPDAC). All participants will be treated until progressive disease or unacceptable toxicity or withdrawal of consent or another discontinuation criterion is met.
Interventions
DRUGAZD0171
AZD0171
DRUGDurvalumab
Durvalumab
DRUGGemcitabine
Chemotherapy (Standard-of-Care)
DRUGNab-paclitaxel
Chemotherapy (Standard-of-Care)
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group performance status of 0 or 1 at screening/enrolment * Must have a Gustave Roussy Immune Score of 0 or 1 * Participants diagnosed with histologically confirmed metastatic pancreatic adenocarcinoma * Participants must have at least 1 measurable lesion to be called a target lesion according to RECIST v1.1 * All participants must consent to providing sufficient archival specimen taken during metastatic stage or fresh tumour specimens for tumoural CD8+ T cell testing for enrolment * Presence of tumoural CD8+ T cells based on a predetermined benchmarked PDAC external sample * Normal organ and bone marrow function measured within 28 days prior to first dose of study intervention * Body weight ≥ 35 kg
Exclusion criteria
* Symptomatic central nervous system metastasis or any history of leptomeningeal disease or cord compression * A participant with an already known sensitising mutation or tumour characteristic for pancreatic cancer for which there is a preferred local standard-of-care treatment * History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention * Any unresolved toxicities ≥ Grade 2 per Common Terminology Criteria for Adverse Events v5.0 from prior therapy (excluding vitiligo, alopecia, controlled diabetes) * History of solid organ transplantation * History of active primary immunodeficiency * Ongoing or an active infection, including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus. A negative COVID-19 PCR test taken within 28 days of the start of the study treatment is required. * Uncontrolled intercurrent illness * Participants with prior history of myocardial infarction, transient ischemic attack, coronary bypass, or stroke within the past 3 months prior to the first dose of study intervention * Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms * Active or prior documented autoimmune or inflammatory disorders * History of another primary malignancy * Receipt of any conventional or investigational anticancer therapy prior to the scheduled first dose of study intervention * Prior receipt of any immune-mediated therapy * Use of immunosuppressive medication within 14 days prior to the first dose of study intervention * Receipt of live, attenuated vaccine within 28 days prior to the first dose of study intervention (Participants can receive non-live COVID-19 vaccines, at the discretion of the Investigator)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 12 Months (OS-12) | At 12 months | Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months. |
| Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | From Cycle 1 Day 1 (each cycle was 28 days in length) until Day 90 (post last dose of study intervention), up to 34 months | The safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy) was assessed. The grading scales found in the revised National Cancer Institute CTCAE latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL); Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171 | Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length) | The AUCtau of AZD0171 was determined. |
| Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel | Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length) | The AUCtau of Nab-paclitaxel was determined. |
| Clearance (CL) of AZD0171 | Cycle 1 Day 1 and Cycle 4 and Day 1 (each cycle is 28 days in length) | The CL of AZD0171 was determined. |
| Objective Response Rate (ORR) | From Cycle 1 Day 1 (each cycle was 28 days in length) until initiation of subsequent anti-cancer treatment and prior to progression (up to 35 months). | The ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) that occurred prior to the initiation of subsequent anti-cancer treatment and prior to progression. The ORR was assessed per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. |
| Disease Control Rate (DCR) | Up to 16 weeks | The DCR is defined as the percentage of participants with a best overall response of confirmed CR or PR, or who had stable disease (SD) maintained for 16 weeks from first dose. DCR was assessed per RECIST v1.1 criteria. |
| Duration of Response (DoR) | From screening until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months) | The DoR is defined as the time from first documented objective response (confirmed CR or confirmed PR) until date of first documented disease progression or death (by any cause in the absence of disease progression). The DoR was assessed per RECIST v1.1 criteria. |
| Median Progression Free Survival (PFS) | From first dose of study intervention until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months) | The PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), whichever was earlier. The PFS was analyzed using the Kaplan-Meier method. |
| Progression Free Survival at 4 Months (PFS-4) | At 4 months | The percentage of participants alive and free of progression at 4 months per Kaplan-Meier estimate. |
| Median Overall Survival (OS) | From first dose of study intervention until death (Up to 35 months) or from first dose of study intervention until last evaluable assessment (Up to 35 months) | The OS is defined as the time from the start of study intervention to the date of death due to any cause. |
| Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Day 1 of each Cycle through Cycle 27 (each cycle was 28 days in length), at end of treatment and at Day 28 follow up (post last dose); up to 35 months | Mean change from baseline was assessed for serum CA19-9 |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months | Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve. |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months | Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve. |
| Maximum Observed Plasma Concentration (Cmax) of AZD0171 | Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length) | The maximum concentration of AZD0171 was determined. |
| Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel | Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length) | The Cmax of Nab-paclitaxel was determined. |
| Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD0171 | Cycle 1 Day 1 (each cycle is 28 days in length) | The AUCinf of AZD0171 was determined. |
| Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171 | Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length) | The AUClast of AZD0171 was determined. |
| Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel | Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length) | The AUClast of Nab-paclitaxel was determined. |
| Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel | Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length) | The t1/2λz of Nab-paclitaxel was determined. |
| Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region | In cycle 3 (each cycle was 28 days in length), subsequent to the first disease assessment scan conducted at roughly 8 weeks. | The changes in CD8+ T cell tumour infiltration (on-treatment during cycle 3 minus baseline) associated with AZD0171 treatment in combination with durvalumab and chemotherapy was assessed in participants with 1L metastatic pancreatic ductal adenocarcinoma. |
| Clearance (CL) of Nab-paclitaxel | Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length) | The CL of Nab-paclitaxel was determined. |
| Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15, Cycle 3 Day 1 and Day 15, Cycle 4 Day 1 and Day 15, Cycle 5Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1 and Cycle 11 Day 1 (each cycle is 28 days in length) | Serum concentration of LIF bound to AZD0171 (total LIF) was assessed. |
| Terminal Elimination Half-life (t1/2λz) of AZD0171 | Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length) | The t1/2λz of AZD0171 was determined. |
Countries
Canada, South Korea, Spain, United States
Participant flow
Recruitment details
The study enrolled participants across 39 sites in 4 countries. The enrollment period began on December 10, 2021, and the analyses presented in this form are based on clinical data lock date of November 16, 2024.
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All the study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| AZD0171 + Durvalumab + Chemotherapy Participants received AZD0171 (intravenous \[IV\]) along with durvalumab IV in combination with standard-of-care chemotherapy IV (gemcitabine and nab-paclitaxel) until disease progression, death, lost to follow-up or consent withdrawal which ever occurred first. | 126 |
| Total | 126 |
Baseline characteristics
| Characteristic | AZD0171 + Durvalumab + Chemotherapy |
|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 Participants |
| Race/Ethnicity, Customized Missing | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 110 Participants |
| Race/Ethnicity, Customized Not Reported | 6 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants |
| Race/Ethnicity, Customized White | 94 Participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 76 / 126 |
| other Total, other adverse events | 126 / 126 |
| serious Total, serious adverse events | 72 / 126 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs)
The safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy) was assessed. The grading scales found in the revised National Cancer Institute CTCAE latest version was utilized for all events with an assigned CTCAE grading. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL); Grade 4: Life-threatening, urgent intervention required; Grade 5: Death related to AE.
Time frame: From Cycle 1 Day 1 (each cycle was 28 days in length) until Day 90 (post last dose of study intervention), up to 34 months
Population: Safety set, which included all participants who received any amount of study treatment.~As specified in the below data table, in the row entitled, 'Any AE leading to dose reduction of AZD0171', one participant had recorded one reduced dose event of AZD0171 by error. This event was not a dose reduction; but, the study treatment was interrupted due to an AE of infusion related reaction, therefore only partial dose was administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death | 15 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of AZD0171 | 32 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any immune mediated AEs | 45 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to drug interruption of treatment | 36 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to drug interruption of AZD0171 | 33 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to drug interruption of Durvalumab | 24 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to drug interruption of Nab-paclitaxel | 34 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to drug interruption of Gemcitabine | 35 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose reduction of treatment | 2 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose reduction of AZD0171 | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose reduction of Durvalumab | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose reduction of Nab-paclitaxel | 2 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose reduction of Gemcitabine | 2 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose modification of treatment | 36 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose modification of AZD0171 | 33 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose modification of Durvalumab | 24 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose modification of Nab-paclitaxel | 34 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to dose modification of Gemcitabine | 35 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to hospitalisation | 71 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any infusion reaction AEs | 11 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE | 126 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE possibly related to treatment | 123 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE possibly related to AZD0171 | 99 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE possibly related to Durvalumab | 107 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE possibly related to Nab-paclitaxel | 123 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE possibly related to Gemcitabine | 21 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE possibly related to Gemcitabine | 122 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 | 115 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= CTCAE grade 3, possibly related to treatment | 90 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= CTCAE grade 3, possibly related to AZD0171 | 46 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= CTCAE grade 3, possibly related to Durvalumab | 45 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= CTCAE grade 3, possibly related to Nab-paclitaxel | 82 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE of >= CTCAE grade 3, possibly related to Gemcitabine | 84 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE (Serious Adverse Event) | 72 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE possibly related to treatment | 30 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE possibly related to AZD0171 | 14 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE possibly related to Durvalumab | 17 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE possibly related to Nab-paclitaxel | 20 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3 | 70 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3, possibly related to treatment | 27 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3, possibly related to AZD0171 | 11 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3, possibly related to Durvalumab | 16 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3, possibly related to Nab-paclitaxel | 16 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE of >= CTCAE grade 3, possibly related to Gemcitabine | 17 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death, possibly related to treatment | 3 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death, possibly related to AZD0171 | 3 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death, possibly related to Durvalumab | 2 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death, possibly related to Nab-paclitaxel | 3 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE with outcome death, possibly related to Gemcitabine | 3 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of treatment | 37 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Durvalumab | 31 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Nab-paclitaxel | 31 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Gemcitabine | 32 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of treatment, possibly related to treatment | 22 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of AZD0171, possibly related to AZD0171 | 11 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Durvalumab, possibly related to Durvalumab | 12 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Nab-paclitaxel, possibly related to Nab-paclitaxel | 9 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to discontinuation of Gemcitabine, possibly related to Gemcitabine | 11 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to drug interruption of treatment | 103 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to drug interruption of AZD0171 | 86 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to drug interruption of Durvalumab | 61 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to drug interruption of Nab-paclitaxel | 98 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to drug interruption of Gemcitabine | 94 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose reduction of treatment | 67 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose reduction of AZD0171 | 1 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose reduction of Durvalumab | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose reduction of Nab-paclitaxel | 60 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose reduction of Gemcitabine | 54 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose modification of treatment | 110 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose modification of AZD0171 | 86 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose modification of Durvalumab | 61 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose modification of Nab-paclitaxel | 106 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any AE leading to dose modification of Gemcitabine | 100 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of treatment | 28 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of AZD0171 | 27 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Durvalumab | 28 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Nab-paclitaxel | 26 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Gemcitabine | 27 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of treatment, possibly related to treatment | 13 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of AZD0171, possibly related to AZD0171 | 7 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Durvalumab, possibly related to Durvalumab | 10 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Nab-paclitaxel, possibly related to Nab-paclitaxel | 5 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Adverse Events (AEs), Immune Mediated AEs (imAEs) and Serious AEs (SAEs) | Any SAE leading to discontinuation of Gemcitabine, possibly related to Gemcitabine | 6 Participants |
Primary
Overall Survival at 12 Months (OS-12)
Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months.
Time frame: At 12 months
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Overall Survival at 12 Months (OS-12) | 53.8 Percentage |
Secondary
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD0171
The AUCinf of AZD0171 was determined.
Time frame: Cycle 1 Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) of AZD0171 | 56570 h*ug/mL | Geometric Coefficient of Variation 77.33 |
Secondary
Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171
The AUClast of AZD0171 was determined.
Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171 | AUClast Cycle 01 Day 01 | 38600 h*ug/mL | Geometric Coefficient of Variation 87.5 |
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of AZD0171 | AUClast Cycle 04 Day 01 | 66290 h*ug/mL | Geometric Coefficient of Variation 44.47 |
Secondary
Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel
The AUClast of Nab-paclitaxel was determined.
Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel | AUClast Cycle 01 Day 15 | 3992 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 63.7 |
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUClast) of Nab-paclitaxel | AUClast Cycle 04 Day 15 | 2853 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 107.7 |
Secondary
Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171
The AUCtau of AZD0171 was determined.
Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171 | AUCtau Cycle 01 Day 01 | 43770 hour*microgram/milliliter (h*ug/mL) | Geometric Coefficient of Variation 55.76 |
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of AZD0171 | AUCtau Cycle 04 Day 01 | 81760 hour*microgram/milliliter (h*ug/mL) | Geometric Coefficient of Variation 14.11 |
Secondary
Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel
The AUCtau of Nab-paclitaxel was determined.
Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel | AUCtau Cycle 01 Day 15 | 4550 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 54.03 |
| AZD0171 + Durvalumab + Chemotherapy | Area Under the Concentration-time Curve in the Dose Interval (AUCtau) of Nab-paclitaxel | AUCtau Cycle 04 Day 15 | 3302 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 98.07 |
Secondary
Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9)
Mean change from baseline was assessed for serum CA19-9
Time frame: Day 1 of each Cycle through Cycle 27 (each cycle was 28 days in length), at end of treatment and at Day 28 follow up (post last dose); up to 35 months
Population: The Pharmacodynamic (PD) set, which included all participants who received any amount of study treatment with at least one reportable PD measurement. The number analyzed n refers to the number of participants included in analysis in specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 26 Day 01 | 0 Units/milliliter (U/mL) | — |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 27 Day 01 | 0 Units/milliliter (U/mL) | — |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | End of treatment | -471.3 Units/milliliter (U/mL) | Standard Deviation 145796.2 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Day 28 Follow up | 19574.2 Units/milliliter (U/mL) | Standard Deviation 114348.1 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 01 Day 01 | 0.0 Units/milliliter (U/mL) | Standard Deviation 0 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 02 Day 01 | -12717.2 Units/milliliter (U/mL) | Standard Deviation 95596.8 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 03 Day 01 | -17463.4 Units/milliliter (U/mL) | Standard Deviation 99400.5 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 04 Day 01 | -19283.0 Units/milliliter (U/mL) | Standard Deviation 106081.2 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 05 Day 01 | -19823.2 Units/milliliter (U/mL) | Standard Deviation 109490 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 06 Day 01 | -21974.6 Units/milliliter (U/mL) | Standard Deviation 115724.1 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 07 Day 01 | -25249.6 Units/milliliter (U/mL) | Standard Deviation 124848.3 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 08 Day 01 | -26902.4 Units/milliliter (U/mL) | Standard Deviation 129722 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 09 Day 01 | -12230.2 Units/milliliter (U/mL) | Standard Deviation 31705.4 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 10 Day 01 | -570.9 Units/milliliter (U/mL) | Standard Deviation 29271.1 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 11 Day 01 | -3363.4 Units/milliliter (U/mL) | Standard Deviation 6647.6 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 12 Day 01 | -3469.5 Units/milliliter (U/mL) | Standard Deviation 6766.1 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 13 Day 01 | -2674.8 Units/milliliter (U/mL) | Standard Deviation 6895.7 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 14 Day 01 | -3100.1 Units/milliliter (U/mL) | Standard Deviation 6768.7 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 15 Day 01 | -1229.7 Units/milliliter (U/mL) | Standard Deviation 2027.1 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 16 Day 01 | -1346.8 Units/milliliter (U/mL) | Standard Deviation 2040.8 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 17 Day 01 | -1470.2 Units/milliliter (U/mL) | Standard Deviation 2171.6 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 18 Day 01 | -1867.5 Units/milliliter (U/mL) | Standard Deviation 2666 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 19 Day 01 | -1868.8 Units/milliliter (U/mL) | Standard Deviation 2691.3 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 20 Day 01 | -1928.7 Units/milliliter (U/mL) | Standard Deviation 3255.2 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 21 Day 01 | -1830.8 Units/milliliter (U/mL) | Standard Deviation 2663.2 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 22 Day 01 | -1903.7 Units/milliliter (U/mL) | Standard Deviation 3244.6 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 23 Day 01 | -1854.3 Units/milliliter (U/mL) | Standard Deviation 3240.4 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 24 Day 01 | -2764.5 Units/milliliter (U/mL) | Standard Deviation 3909.6 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Baseline in Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) | Cycle 25 Day 01 | 0.9 Units/milliliter (U/mL) | — |
Secondary
Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region
The changes in CD8+ T cell tumour infiltration (on-treatment during cycle 3 minus baseline) associated with AZD0171 treatment in combination with durvalumab and chemotherapy was assessed in participants with 1L metastatic pancreatic ductal adenocarcinoma.
Time frame: In cycle 3 (each cycle was 28 days in length), subsequent to the first disease assessment scan conducted at roughly 8 weeks.
Population: The PD set, which included all participants who received any amount of study treatment with at least one reportable PD measurement. The number analyzed n refers to the number of participants included in analysis in specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region | Central tumor region | 2.86 Cells/millimeter square | Standard Deviation 378.12 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region | Central tumor region - within Pan-cytokeratin (PanCK)- Tumor Stroma Area | -10.66 Cells/millimeter square | Standard Deviation 460.92 |
| AZD0171 + Durvalumab + Chemotherapy | Change From Screening in Cluster of Differentiation 8 (CD8+) T Cell Tumour Infiltration in Central Tumour Region | Central tumor region- within PanCK+ Carcinoma Cell Compartment | -25.68 Cells/millimeter square | Standard Deviation 329 |
Secondary
Clearance (CL) of AZD0171
The CL of AZD0171 was determined.
Time frame: Cycle 1 Day 1 and Cycle 4 and Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Clearance (CL) of AZD0171 | Cycle 01 Day 01 | 0.02651 Liter/hour (L/h) | Geometric Coefficient of Variation 77.33 |
| AZD0171 + Durvalumab + Chemotherapy | Clearance (CL) of AZD0171 | Cycle 04 Day 01 | 0.01835 Liter/hour (L/h) | Geometric Coefficient of Variation 14.11 |
Secondary
Clearance (CL) of Nab-paclitaxel
The CL of Nab-paclitaxel was determined.
Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Population: PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Clearance (CL) of Nab-paclitaxel | Cycle 1 Day 15 | 51.37 Liter/hour/meter square (L/h/m**2) | Geometric Coefficient of Variation 67.48 |
| AZD0171 + Durvalumab + Chemotherapy | Clearance (CL) of Nab-paclitaxel | Cycle 4 Day 15 | 67.13 Liter/hour/meter square (L/h/m**2) | Geometric Coefficient of Variation 99.7 |
Secondary
Disease Control Rate (DCR)
The DCR is defined as the percentage of participants with a best overall response of confirmed CR or PR, or who had stable disease (SD) maintained for 16 weeks from first dose. DCR was assessed per RECIST v1.1 criteria.
Time frame: Up to 16 weeks
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Disease Control Rate (DCR) | 65.9 Percentage |
Secondary
Duration of Response (DoR)
The DoR is defined as the time from first documented objective response (confirmed CR or confirmed PR) until date of first documented disease progression or death (by any cause in the absence of disease progression). The DoR was assessed per RECIST v1.1 criteria.
Time frame: From screening until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months)
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Duration of Response (DoR) | 7.72 Months |
Secondary
Maximum Observed Plasma Concentration (Cmax) of AZD0171
The maximum concentration of AZD0171 was determined.
Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the noncompartmental analysis (NCA). Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Maximum Observed Plasma Concentration (Cmax) of AZD0171 | Cycle 01 Day 01 | 395.4 microgram/mililiter (ug/mL) | Geometric Coefficient of Variation 16.84 |
| AZD0171 + Durvalumab + Chemotherapy | Maximum Observed Plasma Concentration (Cmax) of AZD0171 | Cycle 04 Day 01 | 694.6 microgram/mililiter (ug/mL) | Geometric Coefficient of Variation 31.62 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel
The Cmax of Nab-paclitaxel was determined.
Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel | Cycle 01 Day 15 | 1996 nanogram/mililiter (ng/ml) | Geometric Coefficient of Variation 176.4 |
| AZD0171 + Durvalumab + Chemotherapy | Maximum Observed Plasma Concentration (Cmax) of Nab-paclitaxel | Cycle 04 Day 15 | 1113 nanogram/mililiter (ng/ml) | Geometric Coefficient of Variation 553.2 |
Secondary
Median Overall Survival (OS)
The OS is defined as the time from the start of study intervention to the date of death due to any cause.
Time frame: From first dose of study intervention until death (Up to 35 months) or from first dose of study intervention until last evaluable assessment (Up to 35 months)
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Median Overall Survival (OS) | 13.67 Months |
Secondary
Median Progression Free Survival (PFS)
The PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death (by any cause in the absence of progression), whichever was earlier. The PFS was analyzed using the Kaplan-Meier method.
Time frame: From first dose of study intervention until disease progression or last evaluable assessment in the absence of progression, whichever came first (up to 35 months)
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Median Progression Free Survival (PFS) | 7.33 Months |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum
Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve.
Time frame: Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months
Population: Immunogenicity set, which included all participants who received at least one dose of investigational product (IP) with at least one reportable immunogenicity assessment. The number analyzed n refers to the number of participants included in analysis of specific ADA category as mentioned below, \[a\] Participants with ADA result at baseline and/or post-baseline \[b\] Participants with ADA result at baseline and ≥1 post-baseline \[c\] Participants with ADA result at baseline only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | ADA positive at baseline and/or post-baseline (ADA prevalence) (a) | 2 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Treatment Emergent-ADA positive AZD0171 | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Treatment-induced ADA positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Treatment-boosted ADA positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Both baseline and post-baseline positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | Only baseline positive (c) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | ADA persistently positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against AZD0171 in Serum | ADA transiently positive (b) | 0 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum
Number and percentage of participants in the below categories are provided:(i)ADA positive (+ve) at baseline and/or post-baseline visits. The percentage of these participants in a population is known as ADA prevalence(ii)ADA +ve post-baseline and not detected at baseline (treatment-induced ADA positive)(iii)Treatment-boosted ADA +ve:Baseline +ve ADA titre-boosted to a 4-fold or higher level following drug administration(iv)Treatment-emergent ADA +ve:The sum of treatment-induced ADA +ve and treatment-boosted ADA +ve. The percentage of these participants in a population is known as ADA incidence(v)Persistent +ve:ADA negative (-ve) at baseline and having at least 2 post-baseline ADA +ve measurements with ≥ 16 weeks between first and last positive, or an ADA +ve result at the last available post-baseline assessment(vi)Transient +ve:ADA -ve at baseline and at least 1 post-baseline ADA +ve measurement and not fulfilling the conditions for persistently +ve.
Time frame: Cycle 1 (Days 1 and 15), Cycle 2 (Days 1 and 15), until Day 90 post last dose of study intervention (each cycle is 28 days in length), assessed up to 35 months
Population: Immunogenicity set, which included all participants who received at least one dose of IP with at least one reportable immunogenicity assessment. The number analyzed n refers to the number of participants included in analysis of specific ADA category as mentioned below, \[a\] Number of participants with ADA result at baseline and/or post-baseline \[b\] Number of participants with ADA result at baseline and ≥1 post-baseline \[c\] Number of participants with ADA result at baseline only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | ADA positive at baseline and/or post-baseline (ADA prevalence) (a) | 8 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Treatment Emergent-ADA positive (ADA incidence) (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Treatment-induced ADA positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Treatment-boosted ADA positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Both baseline and post-baseline positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | Only baseline positive (c) | 3 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | ADA persistently positive (b) | 0 Participants |
| AZD0171 + Durvalumab + Chemotherapy | Number of Participants With Positive Anti-drug Antibodies (ADAs) Against Durvalumab in Serum | ADA transiently positive (b) | 0 Participants |
Secondary
Objective Response Rate (ORR)
The ORR is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) that occurred prior to the initiation of subsequent anti-cancer treatment and prior to progression. The ORR was assessed per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
Time frame: From Cycle 1 Day 1 (each cycle was 28 days in length) until initiation of subsequent anti-cancer treatment and prior to progression (up to 35 months).
Population: Response Evaluable Set (RES), which included all participants who had measurable disease at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Objective Response Rate (ORR) | 34.9 Percentage |
Secondary
Progression Free Survival at 4 Months (PFS-4)
The percentage of participants alive and free of progression at 4 months per Kaplan-Meier estimate.
Time frame: At 4 months
Population: The ITT set, which included all participants who received any dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Progression Free Survival at 4 Months (PFS-4) | 75.5 Percentage |
Secondary
Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time
Serum concentration of LIF bound to AZD0171 (total LIF) was assessed.
Time frame: Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15, Cycle 3 Day 1 and Day 15, Cycle 4 Day 1 and Day 15, Cycle 5Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1 and Cycle 11 Day 1 (each cycle is 28 days in length)
Population: The PD set, which included all participants who received any amount of study treatment with at least one reportable PD measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 01 Day 01 | 82.01 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 55.91 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 01 Day 15 | 284.6 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 93.92 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 02 Day 01 | 195.5 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 85.89 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 02 Day 15 | 174.9 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 69.12 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 03 Day 01 | 201.4 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 106.4 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 03 Day 15 | 169.2 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 63.66 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 04 Day 01 | 166.2 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 59.66 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 04 Day 15 | 139.5 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 71.98 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 05 Day 01 | 169.2 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 71.97 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 06 Day 01 | 182.5 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 96.65 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 07 Day 01 | 310.0 picogram/millilitre (pg/mL) | — |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 08 Day 01 | 187.8 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 94.74 |
| AZD0171 + Durvalumab + Chemotherapy | Serum Concentration of Total Leukaemia Inhibitory Factor (LIF) Over Time | Cycle 11 Day 01 | 133.2 picogram/millilitre (pg/mL) | Geometric Coefficient of Variation 50.24 |
Secondary
Terminal Elimination Half-life (t1/2λz) of AZD0171
The t1/2λz of AZD0171 was determined.
Time frame: Cycle 1 Day 1 and Cycle 4 Day 1 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Terminal Elimination Half-life (t1/2λz) of AZD0171 | Cycle 04 Day 01 | 188.2 Hours | Geometric Coefficient of Variation 6.567 |
| AZD0171 + Durvalumab + Chemotherapy | Terminal Elimination Half-life (t1/2λz) of AZD0171 | Cycle 01 Day 01 | 127.4 Hours | Geometric Coefficient of Variation 77.48 |
Secondary
Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel
The t1/2λz of Nab-paclitaxel was determined.
Time frame: Cycle 1 Day 15 and Cycle 4 Day 15 (each cycle is 28 days in length)
Population: The PK set which included all participants who received any amount of study treatment with at least one reportable PK measurement. The number analyzed, 'n', refers to participants with intensive PK sampling at specific time points, who were included in the NCA. Additional population PK/PK analyses are available under reference: 39041713.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD0171 + Durvalumab + Chemotherapy | Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel | Cycle 1 Day 15 | 7.353 Hours | Geometric Coefficient of Variation 85.14 |
| AZD0171 + Durvalumab + Chemotherapy | Terminal Elimination Half-life (t1/2λz) of Nab-paclitaxel | Cycle 4 Day 15 | 9.509 Hours | Geometric Coefficient of Variation 20.2 |