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

May 8, 2026 updated by: AstraZeneca

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

403

Phase

  • 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
      • Kogarah, Australia, 2217
        • Recruiting
        • Research Site
      • Melbourne, Australia, 3000
        • Recruiting
        • Research Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Recruiting
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X6
        • Recruiting
        • Research Site
  • China
      • Beijing, China, 100142
        • Not yet recruiting
        • Research Site
      • Beijing, China, 100142
        • Recruiting
        • Research Site
      • Chongqing, China, 400030
        • Recruiting
        • Research Site
      • Guangzhou, China, 510100
        • Recruiting
        • Research Site
      • Harbin, China, 150049
        • Not yet recruiting
        • Research Site
      • Wuhan, China, 430022
        • Recruiting
        • Research Site
  • France
      • Marseille, France, 13385
        • Recruiting
        • Research Site
      • Rennes, France, 35000
        • Recruiting
        • Research Site
      • Villejuif, France, 94805
        • Recruiting
        • Research Site
  • Italy
      • Milan, Italy, 20162
        • Recruiting
        • Research Site
      • Orbassano, Italy, 10043
        • Recruiting
        • Research Site
      • Rozzano, Italy, 20089
        • Recruiting
        • Research Site
      • Verona, Italy, 37134
        • Recruiting
        • Research Site
  • Japan
      • Chūōku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • Research Site
      • Kōtoku, Japan, 135-8550
        • Recruiting
        • Research Site
      • Osaka, Japan, 541-8567
        • Recruiting
        • Research Site
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • Recruiting
        • Research Site
      • Kuching, Malaysia, 93586
        • Recruiting
        • Research Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Recruiting
        • Research Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Research Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 8035
        • Recruiting
        • Research Site
      • Madrid, Spain, 28040
        • Recruiting
        • Research Site
      • Seville, Spain, 41013
        • Recruiting
        • Research Site
  • Taiwan
      • Taichung, Taiwan, 40705
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 11217
        • Recruiting
        • Research Site
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Research Site
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • Research Site
      • Irvine, California, United States, 92618
        • Withdrawn
        • Research Site
    • Connecticut
      • North Haven, Connecticut, United States, 06473
        • Recruiting
        • Research Site
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20016
        • Recruiting
        • Research Site
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Not yet recruiting
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Recruiting
        • Research Site
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Research Site
    • Massachusetts
      • Milford, Massachusetts, United States, 01757
        • Recruiting
        • Research Site
    • New York
      • Mineola, New York, United States, 11501
        • Recruiting
        • Research Site
      • New York, New York, United States, 10021
        • Recruiting
        • Research Site
      • New York, New York, United States, 10016
        • Recruiting
        • Research Site
      • New York, New York, United States, 10029
        • Recruiting
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Research Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • 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
  • 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

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: Bevacizumab
IV infusion
Drug: Leucovorin
IV infusion
Drug: AZD9592
Varying doses of AZD9592
Drug: 5-Fluorouracil (5-FU)
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From time of Informed Consent to 30 days post last dose of AZD9592
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
From time of Informed Consent to 30 days post last dose of AZD9592
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
From time of Informed Consent to 30 days post last dose of AZD9592
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)
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
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
From time of first dose of AZD9592 to end of DLT period (approximately 21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
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
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
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
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)
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
From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years)
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.
From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years)
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
From date of first dose of AZD9592 up until 30 days post last dose
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)
From date of first dose of AZD9592 up until 30 days post last dose
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)
From date of first dose of AZD9592 up until 30 days post last dose
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)
From date of first dose of AZD9592 up until 30 days post last dose
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)
From date of first dose of AZD9592 up until 30 days post last dose
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)
From date of first dose of AZD9592 up until 30 days post last dose
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
From date of first dose of AZD9592 up until 30 days post last dose

Collaborators and Investigators

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

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Charu Aggarwal, MD, MPH, University of Pennsylvania

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)

December 21, 2022

Primary Completion (Estimated)

August 2, 2028

Study Completion (Estimated)

August 2, 2028

Study Registration Dates

First Submitted

November 18, 2022

First Submitted That Met QC Criteria

December 2, 2022

First Posted (Actual)

December 12, 2022

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D9350C00001
  • 2022-501570-18-00 (Registry Identifier: CTIS (EU))

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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