Safety, Pharmacokinetics And Clinical Activity Of AZD0171 In Combination With Durvalumab And Chemotherapy In Locally Advanced Or Metastatic Solid Tumours

Study Overview

Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours

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).

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.

Locally Advanced or Metastatic Solid Tumours

DRUG: AZD0171
DRUG: Durvalumab
DRUG: Gemcitabine
DRUG: Nab-paclitaxel

D8151C00001
2021-002040-78 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-08-03	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-23
First Submitted that Met QC Criteria 2021-08-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-24
First Posted (ACTUAL) 2021-08-11	Results First Posted N/A	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: AZD0171 + Durvalumab + chemotherapy Participants will receive AZD0171 (intravenous [IV]) along with durvalumab (IV) in combination with standard-of-care chemotherapy IV (gemcitabine and nab-paclitaxel).	DRUG: AZD0171 AZD0171 DRUG: Durvalumab Durvalumab DRUG: Gemcitabine Chemotherapy (Standard-of-Care) DRUG: Nab-paclitaxel Chemotherapy (Standard-of-Care)

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: AZD0171 + Durvalumab + chemotherapy

Participants will receive AZD0171 (intravenous [IV]) along with durvalumab (IV) in combination with standard-of-care chemotherapy IV (gemcitabine and nab-paclitaxel).

DRUG: AZD0171

AZD0171

DRUG: Durvalumab

Durvalumab

DRUG: Gemcitabine

Chemotherapy (Standard-of-Care)

DRUG: Nab-paclitaxel

Chemotherapy (Standard-of-Care)

Primary Outcome Measures	Measure Description	Time Frame
Number of participants with adverse events (AEs), immune mediated AEs (imAEs) and serious AEs (SAEs)	Assessment of safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy).	Until Day 90 (post last dose of study intervention on Day 15)
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.	Up to 12 months

Secondary Outcome Measures	Measure Description	Time Frame
Objective response rate (ORR)	Assessment of efficacy of study intervention according to Response Evaluation Criteria in Solid Tumours (RECIST 1.1) using investigator assessment of disease response. The percentage of response evaluable participants with a confirmed response of complete response (CR) or partial response (PR).	Up to 24 months
Disease control rate (DCR)	Assessment of the efficacy of study intervention according to RECIST v1.1. The DCR is defined as the percentage of participants according to RECIST v1.1 with a confirmed response or stable disease maintained for 16 weeks.	Up to 24 months
Duration of response (DoR)	Assessment of the efficacy of study intervention according to RECIST 1.1. The DoR is defined as the time from first documented response until date of documented disease progression or death.	Up to 24 months
Median progression free survival (PFS)	PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death.	Up to 24 months
PFS at 4 months (PFS-4)	Percentage of participants free of progression at 4 months per Kaplan-Meier estimate.	4 months
Median overall survival (OS)	OS is defined as the time from the start of study intervention to the date of death due to any causes.	Up to 24 months
Number of participants with change from Baseline in serum levels of carbohydrate antigen 19-9 (CA19-9)	Percentage change in local laboratory assessed serum CA19-9 from baseline.	From Screening (Day -28 to Day -1) until Day 28 post last dose of study intervention on Day 15
Number of participants developing detectable anti-drug antibodies (ADAs) against AZD0171 and/or durvalumab in serum	Immunogenicity of AZD0171 and/or durvalumab will be assessed.	Up to Day 90 post last dose of study intervention on Day 15
The PK profile of AZD0171, durvalumab and chemotherapy- Maximum observed plasma concentration (Cmax)	The PK profile of AZD0171, durvalumab and chemotherapies and/or their metabolites will be determined.	At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
The PK profile of AZD0171, durvalumab and chemotherapy - Area under the concentration-time curve (AUC)	The PK profile of AZD0171, durvalumab and chemotherapies and/or their metabolites will be determined.	At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
The PK profile of AZD0171, durvalumab and chemotherapy - Clearance (CL)	The PK profile of AZD0171, durvalumab and chemotherapies and/or their metabolites will be determined.	At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
The PK profile of AZD0171, durvalumab and chemotherapy - Terminal elimination half-life (t1/2)	The PK profile of AZD0171, durvalumab and chemotherapies and/or their metabolites will be determined.	At predefined intervals from first dose of study intervention up to Day 90 post last dose of study intervention on Day 15
Participants with changes from Baseline in cluster of differentiation 8 (CD8+) T cell tumour infiltration in tumour samples	The changes in CD8+ T cell tumour infiltration associated with AZD0171 treatment in combination with durvalumab and chemotherapy will be assessed in participants with 1L mPDAC.	Up to 24 months
Change from baseline in leukaemia inhibitory factor (LIF) bound to AZD0171 (total LIF)	The absolute values and the change from baseline in LIF bound to AZD0171 (total LIF) will be assessed.	At predefined intervals from first dose of study intervention up to Cycle 11 (each cycle is 28 days in length)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record