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Active, Not Recruiting

NCT Number: NCT05647122

First in Human Study of AZD9592 in 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Advanced Solid Tumours Bronchial Neoplasms Carcinoma Non-small Cell Lung Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Kogarah, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 2 weeks prior to start of study treatment.
  • Participants with cardiac comorbidities as defined in the study protocol

Treatment and study plan

AZD9592

Drug

Varying doses of AZD9592

Osimertinib

Drug

tablets administered orally

5-fluorouracil (5-FU)

Drug

IV infusion

Leucovorin

Drug

IV infusion

Bevacizumab

Drug

IV infusion

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Acronym: EGRET

Important dates

Study start
2022
Primary completion
2028
Study completion
2028
First posted
Dec 12, 2022
Registry last updated
Jun 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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