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

A Phase II Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Participants With 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).

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumours
• Intervention / Treatment: Drug: AZD0171; Drug: Durvalumab; Drug: Gemcitabine; Drug: Nab-paclitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
• Korea, Republic of
  • Seongnam-Si, Korea, Republic of, 463-712
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Seoul, Korea, Republic of, 06591
    • Research Site
• Spain
  • Badalona, Spain, 08916
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • Research Site
    • Los Angeles, California, United States, 90025
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • Ventura, California, United States, 93003
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Research Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Research Site
  • New York
    • Buffalo, New York, United States, 14263
      • Research Site
    • New York, New York, United States, 10065
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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; Other Names: MSC-1; Drug: Durvalumab; Durvalumab; Other Names: MEDI4736; Drug: Gemcitabine; Chemotherapy (Standard-of-Care); Drug: Nab-paclitaxel; Chemotherapy (Standard-of-Care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2021
• Primary Completion (Estimated): October 7, 2024
• Study Completion (Estimated): October 7, 2024

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Immunotherapy; Pancreatic ductal adenocarcinoma; Durvalumab; Nab-paclitaxel; AZD0171; Leukaemia inhibitory factor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Durvalumab; Gemcitabine
• Other Study ID Numbers: D8151C00001; 2021-002040-78 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No