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).

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)