First in Human Study to Evaluate AZD8205 in Patients With Advanced or Metastatic Solid Malignancies

November 23, 2023 updated by: AstraZeneca

A Phase I/IIa Multi-center, Open-label Master Protocol to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of AZD8205 in Participants With Advanced or Metastatic Solid Malignancies

This research study is studying a new compound, AZD8205, as a possible treatment for advanced or metastatic solid tumours

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

248

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia, VIC 3000
        • Recruiting
        • Research Site
      • Nedlands, Australia, 6009
        • Recruiting
        • Research Site
      • South Brisbane, Australia, 4101
        • Withdrawn
        • Research Site
  • Belgium
      • Anderlecht, Belgium, 1070
        • Not yet recruiting
        • Research Site
      • Leuven, Belgium, 3000
        • Not yet recruiting
        • Research Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Not yet recruiting
        • Research Site
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • Research Site
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • Research Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recruiting
        • Research Site
  • China
      • Beijing, China, 100142
        • Recruiting
        • Research Site
      • Changsha, China, 410013
        • Recruiting
        • Research Site
      • Chongqing, China, 400030
        • Recruiting
        • Research Site
      • Guangzhou, China, 510060
        • Recruiting
        • Research Site
  • Hungary
      • Budapest, Hungary, 1083
        • Not yet recruiting
        • Research Site
      • Budapest, Hungary, 1122
        • Not yet recruiting
        • Research Site
      • Budapest, Hungary, 1062
        • Not yet recruiting
        • Research Site
  • Japan
      • Chuo-ku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
      • Koto-ku, Japan, 135-8550
        • Recruiting
        • Research Site
      • Sunto-gun, Japan, 411-8777
        • Not yet recruiting
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Not yet recruiting
        • Research Site
  • Poland
      • Warszawa, Poland, 02-781
        • Not yet recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 8035
        • Not yet recruiting
        • Research Site
      • L'Hospitalet de Llobregat, Spain, 08908
        • Not yet recruiting
        • Research Site
      • Málaga, Spain, 29010
        • Not yet recruiting
        • Research Site
      • Pamplona, Spain, 31008
        • Not yet recruiting
        • Research Site
  • Taiwan
      • Tainan, Taiwan, 704
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 11259
        • Recruiting
        • Research Site
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Not yet recruiting
        • Research Site
      • Chiang Mai, Thailand, 50200
        • Recruiting
        • Research Site
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0XY
        • Recruiting
        • Research Site
      • Cardiff, United Kingdom, CF14 2TL
        • Not yet recruiting
        • Research Site
      • London, United Kingdom, EC1A 7BE
        • Recruiting
        • Research Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • Research Site
      • Irvine, California, United States, 92618
        • Recruiting
        • Research Site
      • Santa Monica, California, United States, 90404
        • Recruiting
        • Research Site
      • Santa Rosa, California, United States, 95403
        • Recruiting
        • Research Site
    • Florida
      • Sarasota, Florida, United States, 34232
        • Withdrawn
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Recruiting
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Research Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Recruiting
        • Research Site
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Not yet recruiting
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Not yet recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Age ≥ 18 years
  • Relapsed/metastatic solid tumors treated with prior adequate standard of care therapy for tumor type and stage of disease or where in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy.
  • Measurable disease per RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
  • Life expectancy ≥ 12 weeks
  • Adequate organ and marrow function as defined in the protocol

For Sub-Study 1 Part A:

• Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer

For Sub-Study 1 Part B:

  • Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort:

    1. Cohort B1 (Biliary Tract Cancer)
    2. Cohort B2 (Ovarian Cancer)
    3. Cohort B3 (Breast Cancer)

    4. Cohort B4 (Endometrial Cancer)

      Exclusion Criteria:

  • Treatment with any of the following:

    1. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment
    2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study treatment

    3. Any other anticancer treatment within the following time periods prior to the first dose of study intervention:

      1. Cytotoxic treatment: 21 days
      2. Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter)
      3. Biological products including immuno-oncology agents: 28 days
  • Spinal cord compression or a history of leptomeningeal carcinomatosis.
  • Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study.
  • Active infection including tuberculosis and HBV, HCV or HIV
  • History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses

  • Participants with any of the following cardiac criteria:

    1. History of arrhythmia which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia.
    2. Uncontrolled hypertension.
    3. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.
    4. History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
    5. Symptomatic heart failure (NYHA class ≥ 2).
    6. Prior or current cardiomyopathy.
    7. Severe valvular heart disease.
    8. Mean resting QTcF > 470 msec.
    9. Risk factors for QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sub-Study 1 AZD8205 Monotherapy

Sub-Study 1 has two parts:

Part A : The aim is to determine the safety, tolerability, Recommended Phase 2 Dose(RP2D), and/or the Maximum Tolerated Dose (MTD) of AZD8205.

Part B: The aim of dose expansion is to evaluate anti-tumor activity of AZD8205 as monotherapy in select solid tumors.
Drug: AZD8205
AZD8205 is an antibody drug conjugate that has the potential to treat a wide variety of solid tumors including but not limited to breast cancer, Biliary Tract Cancer, ovarian, and endometrial cancers

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of patients with adverse events
Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year).
Number of patients with adverse events by system organ class and preferred term
From time of Informed consent to 30 days post last dose (approximately 1 year).
The number of patients with serious adverse events
Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year)
Number of patients with serious adverse events by system organ class and preferred term
From time of Informed consent to 30 days post last dose (approximately 1 year)
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
Time Frame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
A DLT is defined as any toxicity that occurs from the first dose of study treatment up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation and which includes pre-defined haematological and non-haematological toxicities.
From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
The number of patients with changes from baseline laboratory findings, ECGs and vital signs
Time Frame: From time of informed consent to 30 days post last dose (approximately 1 year)
Description of laboratory findings and vital signs variables over time including change from baseline.
From time of informed consent to 30 days post last dose (approximately 1 year)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1).
From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Duration of response (DoR)
Time Frame: From the first documented response to confirmed progressive disease or death ( approx. 2 years )
The time from the date of first response until date of disease progression or death in the absence of disease progression.
From the first documented response to confirmed progressive disease or death ( approx. 2 years )
Progression free Survival (PFS)
Time Frame: From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
The time from first dose until RECIST 1.1 defined disease progression or cessation of study treatment.
From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Disease Control Rate at 12 weeks (DCR-12)
Time Frame: Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
Percentage of patients with confirmed CR or PR or having SD maintained for >= 11 weeks from first dose.
Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
Overall Survival (OS)
Time Frame: From first dose of AZD8205 to death ( approx. 2 years )
The time from the date of the first dose of study treatment until death due to any cause.
From first dose of AZD8205 to death ( approx. 2 years )
Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Area under the plasma concentration-time curve
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Maximum observed plasma concentration of the study drug
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Time to maximum observed plasma concentration of the study drug
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Pharmacokinetics of AZD8205: Clearance
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Terminal elimination half life.
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Immunogenicity of AZD8205.
Time Frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
The number and percentage of participants who develop ADAs.
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )

Collaborators and Investigators

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

Sponsor

AstraZeneca

Publications and helpful links

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

General Publications

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 Major Dates

Study Start (Actual)

October 18, 2021

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

October 13, 2021

First Submitted That Met QC Criteria

November 5, 2021

First Posted (Actual)

November 17, 2021

Study Record Updates

Last Update Posted (Actual)

November 27, 2023

Last Update Submitted That Met QC Criteria

November 23, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D6900C00001
  • 2021-000736-66 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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