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First in Human Study of AZD9592 in Solid Tumors (EGRET)

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: NCT05647122
Recruitment Status : Recruiting
First Posted : December 12, 2022
Last Update Posted : June 4, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a first-in-human (FIH) Phase I, multi-center, open-label, study of AZD9592, in patients with advanced solid tumors. The study consists of several study modules, each evaluating the safety, tolerability, preliminary efficacy, pharmacokinetics (PK), pharmacodynamics, anti-tumor activity, and immunogenicity of AZD9592, as monotherapy or in combination with anti-cancer agents.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Carcinoma Non-small Cell Lung Head and Neck Neoplasms Colorectal Neoplasms Drug: AZD9592 Drug: Osimertinib Drug: 5-Fluorouracil (5-FU) Drug: Leucovorin Drug: Bevacizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumors
Actual Study Start Date : December 22, 2022
Estimated Primary Completion Date : October 29, 2025
Estimated Study Completion Date : October 29, 2025

Arm Intervention/treatment
Experimental: Module 1 AZD9592 Monotherapy

Module 1 has two parts:

Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592.

Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 as monotherapy in select solid tumors

Drug: AZD9592
Varying doses of AZD9592

Experimental: Module 2 AZD9592 Combination with Osimertinib

Module 2 has two parts:

Part A aims to determine the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with Osimertinib.

Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with Osimertinib in NSCLC EGFRm

Drug: AZD9592
Varying doses of AZD9592

Drug: Osimertinib
tablets administered orally

Experimental: Module 3 AZD9592 Combination 5-FU, Bevacizumab, Leucovorin

Module 3 has two parts:

Part A aims to determine the safety, tolerability and/or recommended phase 2 dose (RP2D) of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC) Part B aims to determine the safety, tolerability and evaluate anti-tumor activity of AZD9592 in combination with 5-FU, Bevacizumab, Leucovorin in Colorectal Cancer (CRC)

Drug: AZD9592
Varying doses of AZD9592

Drug: 5-Fluorouracil (5-FU)
IV infusion

Drug: Leucovorin
IV infusion

Drug: Bevacizumab
IV infusion




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
    Number of patients with adverse events by system organ class and preferred term

  2. Incidence of Serious Adverse Events (SAEs) [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
    Number of patients with serious adverse events by system organ class and preferred term

  3. Incidence of dose-limiting toxicities (DLT) as defined in the protocol [ Time Frame: From time of first dose of AZD9592 to end of DLT period (approximately 21 days) ]
    Number of patients with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol

  4. Incidence of baseline laboratory finding, ECG and vital signs changes [ Time Frame: From time of Informed Consent to 30 days post last dose of AZD9592 ]
    measured by laboratory and vital sign variables over time including change from baseline

  5. Proportion of patients with radiological response (ORR) [ Time Frame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years) ]
    Assessed by overall response rate (ORR) defined as the proportion of patients who have a confirmed complete or partial radiological response by the Investigator according to RECIST v1.1 (for patients in the dose expansion cohorts, only)


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years) ]
    The percentage or number of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST v1.1)

  2. Duration of Response (DoR) [ Time Frame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years) ]
    The time from date of first response until date of disease progression or last evaluable assessment (RECIST v1.1) in the absence of progression

  3. Disease Control Rate (DCR) at 12 weeks [ Time Frame: From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks) ]
    The percentage of patients with confirmed CR or PR or having SD maintained (RECIST v1.1) for >=11 weeks from first dose

  4. Progression free Survival (PFS) [ Time Frame: From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years) ]
    The time from first dose until RECIST 1.1 defined disease progression or death due to any cause

  5. Overall Survival (OS) [ Time Frame: From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years) ]
    The time from the date of the first dose of study treatment until death due to any cause.

  6. Pharmacokinetics of AZD9592: Plasma PK concentrations [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of plasma concentrations of AZD9592, total antibody and total unconjugated warhead

  7. Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC) [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of PK parameters: Area under the concentration time curve (AUC)

  8. Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max) [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of PK parameters: Maximum observed plasma concentration of the study drug (C-max)

  9. Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max) [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of PK parameters: Time to maximum observed plasma concentration of the study drug (T-max)

  10. Pharmacokinetics of AZD9592: Clearance [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of PK parameters: the volume of plasma from which the study drug is completely removed per unit time (Clearance)

  11. Pharmacokinetics of AZD9592: Half-life [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Measurement of PK parameters: Terminal elimination half-life (t 1/2)

  12. Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA) [ Time Frame: From date of first dose of AZD9592 up until 30 days post last dose ]
    Evaluating the number and percentage of patients who develop Anti-drug antibody (ADA) during treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
  • Life expectancy ≥ 12 weeks
  • Measurable disease per RECIST v1.1
  • Adequate organ and marrow function as defined in the protocol

Additional Inclusion Criteria for Module 1:

• Histologically or cytologically confirmed metastatic or locally advanced EGFRmut., NSCLC; metastatic EGFRwt. NSCLC; recurrent or metastatic HNSCC of the oral cavity; metastatic CRC.

Additional Inclusion Criteria for Module 2:

• Histologically or cytologically confirmed metastatic NSCLC EGFRmut.

Additional Inclusion Criteria for Module 3:

• Histologically or cytologically confirmed metastatic CRC.

Key Exclusion Criteria:

  • 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.
  • Spinal cord compression or a history of leptomeningeal carcinomatosis.
  • Active infection including tuberculosis and HBV, HCV or HIV
  • Brain metastases unless treated (prior treatment required only for Module 1), 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 treatment.
  • Participants with cardiac comorbidities as defined in the study protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05647122


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, California
Research Site Recruiting
Duarte, California, United States, 91010
Research Site Recruiting
Irvine, California, United States, 92618
United States, Connecticut
Research Site Not yet recruiting
North Haven, Connecticut, United States, 06473
United States, Illinois
Research Site Not yet recruiting
Chicago, Illinois, United States, 60637
United States, Maryland
Research Site Not yet recruiting
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Research Site Recruiting
Milford, Massachusetts, United States, 01757
United States, New York
Research Site Recruiting
Mineola, New York, United States, 11501
Research Site Recruiting
New York, New York, United States, 10016
Research Site Recruiting
New York, New York, United States, 10021
Research Site Not yet recruiting
New York, New York, United States, 10029
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Research Site Recruiting
Providence, Rhode Island, United States, 02903
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Research Site Recruiting
Fairfax, Virginia, United States, 22031
Australia
Research Site Recruiting
Kogarah, Australia, 2217
Research Site Recruiting
Melbourne, Australia, 3000
Canada, Alberta
Research Site Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Research Site Recruiting
Toronto, Ontario, Canada, M5G 1X6
China
Research Site Recruiting
Beijing, China, 100142
Research Site Not yet recruiting
Beijing, China, 100142
Research Site Recruiting
Chongqing, China, 400030
Research Site Recruiting
Guangzhou, China, 510100
Research Site Not yet recruiting
Harbin, China, 150049
Research Site Recruiting
Wuhan, China, 430022
France
Research Site Recruiting
Rennes, France, 35000
Research Site Recruiting
Villejuif Cedex, France, 94805
Italy
Research Site Recruiting
Milano, Italy, 20162
Research Site Recruiting
Orbassano, Italy, 10043
Research Site Recruiting
Rozzano, Italy, 20089
Research Site Recruiting
Verona, Italy, 37134
Japan
Research Site Recruiting
Chuo-ku, Japan, 104-0045
Research Site Recruiting
Kashiwa, Japan, 277-8577
Korea, Republic of
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Research Site Recruiting
Seoul, Korea, Republic of, 03722
Research Site Recruiting
Seoul, Korea, Republic of, 05505
Research Site Recruiting
Seoul, Korea, Republic of, 06351
Malaysia
Research Site Recruiting
Kuching, Malaysia, 93586
Spain
Research Site Recruiting
Barcelona, Spain, 8035
Research Site Recruiting
Madrid, Spain, 28040
Research Site Recruiting
Sevilla, Spain, 41013
Taiwan
Research Site Recruiting
Taichung, Taiwan, 40705
Research Site Recruiting
Taipei City, Taiwan, 11217
Research Site Recruiting
Taipei, Taiwan, 10002
Research Site Recruiting
Taoyuan, Taiwan, 333
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Charu Aggarwal, MD, MPH University of Pennsylvania
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05647122    
Other Study ID Numbers: D9350C00001
First Posted: December 12, 2022    Key Record Dates
Last Update Posted: June 4, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Cancer
First in Human
Antibody Drug Conjugate
Solid Tumour
Phase I
Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Head and Neck Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Bevacizumab
Fluorouracil
Osimertinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents