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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04999969
Recruitment Status : Recruiting
First Posted : August 11, 2021
Last Update Posted : April 12, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 3, 2021
First Posted Date  ICMJE August 11, 2021
Last Update Posted Date April 12, 2023
Actual Study Start Date  ICMJE December 10, 2021
Estimated Primary Completion Date November 14, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
  • Number of participants with adverse events (AEs), immune mediated AEs (imAEs) and serious AEs (SAEs) [ Time Frame: Until Day 90 (post last dose of study intervention on Day 15) ]
    Assessment of safety and tolerability of study intervention (AZD0171, durvalumab, and standard-of-care chemotherapy).
  • Overall survival at 12 months (OS-12) [ Time Frame: Up to 12 months ]
    Percentage of participants alive at 12 months after initiation of study intervention per Kaplan- Meier estimate of OS at 12 months.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2022)
  • Objective response rate (ORR) [ Time Frame: Up to 24 months ]
    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).
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    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.
  • Duration of response (DoR) [ Time Frame: Up to 24 months ]
    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.
  • Median progression free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death.
  • PFS at 4 months (PFS-4) [ Time Frame: 4 months ]
    Percentage of participants free of progression at 4 months per Kaplan-Meier estimate.
  • Median overall survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from the start of study intervention to the date of death due to any causes.
  • Number of participants with change from Baseline in serum levels of carbohydrate antigen 19-9 (CA19-9) [ Time Frame: From Screening (Day -28 to Day -1) until Day 28 post last dose of study intervention on Day 15 ]
    Percentage change in local laboratory assessed serum CA19-9 from baseline.
  • Number of participants developing detectable anti-drug antibodies (ADAs) against AZD0171 and/or durvalumab in serum [ Time Frame: Up to Day 90 post last dose of study intervention on Day 15 ]
    Immunogenicity of AZD0171 and/or durvalumab will be assessed.
  • The PK profile of AZD0171, durvalumab and chemotherapy- Maximum observed plasma concentration (Cmax) [ Time Frame: 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 chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Area under the concentration-time curve (AUC) [ Time Frame: 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 chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Clearance (CL) [ Time Frame: 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 chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Terminal elimination half-life (t1/2) [ Time Frame: 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 chemotherapies and/or their metabolites will be determined.
  • Participants with changes from Baseline in cluster of differentiation 8 (CD8+) T cell tumour infiltration in tumour samples [ Time Frame: Up to 24 months ]
    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.
  • Change from baseline in leukaemia inhibitory factor (LIF) bound to AZD0171 (total LIF) [ Time Frame: At predefined intervals from first dose of study intervention up to Cycle 11 (each cycle is 28 days in length) ]
    The absolute values and the change from baseline in LIF bound to AZD0171 (total LIF) will be assessed.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2021)
  • Objective response rate (ORR) [ Time Frame: Up to 24 months ]
    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).
  • Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    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.
  • Duration of response (DoR) [ Time Frame: Up to 24 months ]
    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.
  • Median progression free survival (PFS) [ Time Frame: Up to 24 months ]
    PFS is defined as the time from first dose of study intervention until the date of objective disease progression or death.
  • PFS at 4 months (PFS-4) [ Time Frame: 4 months ]
    Percentage of participants with PFS at 4 months per Kaplan-Meier estimate of PFS.
  • Median overall survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from the start of study intervention to the date of death due to any cause.
  • Number of participants with change from Baseline in serum levels of carbohydrate antigen 19-9 (CA19-9) [ Time Frame: From Screening (Day -28 to Day -1) until Day 28 post last dose of study intervention on Day 15 ]
    Percentage change in local laboratory assessed serum CA19-9 from baseline.
  • Number of participants developing detectable anti-drug antibodies (ADAs) against AZD0171 and/or durvalumab in serum [ Time Frame: Up to Day 90 post last dose of study intervention on Day 15 ]
    Immunogenicity of AZD0171 and/or durvalumab will be assessed.
  • The PK profile of AZD0171, durvalumab and chemotherapy- Maximum observed plasma concentration (Cmax) [ Time Frame: 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, total leukaemia inhibitory factor (LIF), durvalumab and chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Area under the concentration-time curve (AUC) [ Time Frame: 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, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Clearance (CL) [ Time Frame: 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, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined.
  • The PK profile of AZD0171, durvalumab and chemotherapy - Terminal elimination half-life (t1/2) [ Time Frame: 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, total LIF, durvalumab and chemotherapies and/or their metabolites will be determined.
  • Participants with changes from Baseline in cluster of differentiation 8 (CD8+) T cell tumour infiltration in tumour samples [ Time Frame: Up to 24 months ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics and Clinical Activity of AZD0171 in Combination With Durvalumab and Chemotherapy in Locally Advanced or Metastatic Solid Tumours
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Locally Advanced or Metastatic Solid Tumours
Intervention  ICMJE
  • Drug: AZD0171
    AZD0171
    Other Name: MSC-1
  • Drug: Durvalumab
    Durvalumab
    Other Name: MEDI4736
  • Drug: Gemcitabine
    Chemotherapy (Standard-of-Care)
  • Drug: Nab-paclitaxel
    Chemotherapy (Standard-of-Care)
Study Arms  ICMJE 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).
Interventions:
  • Drug: AZD0171
  • Drug: Durvalumab
  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 3, 2021)		 115
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 14, 2024
Estimated Primary Completion Date November 14, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Canada,   France,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04999969
Other Study ID Numbers  ICMJE D8151C00001
2021-002040-78 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date April 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP