First in Human Study of AZD9592 in Solid Tumors

Colorectal Neoplasms Clinical Trial

— EGRET  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05647122
• Other study ID #: D9350C00001
• Status: Recruiting
• Phase: Phase 1
• Start date: December 22, 2022
• Est. completion date: October 29, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: October 29, 2025
• Est. primary completion date: October 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumours
• Colorectal Neoplasms
• Head and Neck Neoplasms
• Neoplasms

Intervention

Drug:
• AZD9592
Varying doses of AZD9592
• Osimertinib
tablets administered orally
• 5-Fluorouracil (5-FU)
IV infusion
• Leucovorin
IV infusion
• Bevacizumab
IV infusion

Locations

Country	Name	City	State
Australia	Research Site	Kogarah
Australia	Research Site	Melbourne
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Toronto	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Harbin
China	Research Site	Wuhan
France	Research Site	Rennes
France	Research Site	Villejuif Cedex
Italy	Research Site	Milano
Italy	Research Site	Orbassano
Italy	Research Site	Rozzano
Italy	Research Site	Verona
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	Kuching
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
United States	Research Site	Baltimore	Maryland
United States	Research Site	Chicago	Illinois
United States	Research Site	Duarte	California
United States	Research Site	Fairfax	Virginia
United States	Research Site	Houston	Texas
United States	Research Site	Irvine	California
United States	Research Site	Milford	Massachusetts
United States	Research Site	Mineola	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	North Haven	Connecticut
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (AEs)	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
Primary	Incidence of Serious Adverse Events (SAEs)	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
Primary	Incidence of dose-limiting toxicities (DLT) as defined in the protocol	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)
Primary	Incidence of baseline laboratory finding, ECG and vital signs changes	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
Primary	Proportion of patients with radiological response (ORR)	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)
Secondary	Objective Response Rate (ORR)	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)
Secondary	Duration of Response (DoR)	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)
Secondary	Disease Control Rate (DCR) 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)
Secondary	Progression free Survival (PFS)	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)
Secondary	Overall Survival (OS)	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)
Secondary	Pharmacokinetics of AZD9592: Plasma PK concentrations	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
Secondary	Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC)	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
Secondary	Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max)	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
Secondary	Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max)	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
Secondary	Pharmacokinetics of AZD9592: Clearance	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
Secondary	Pharmacokinetics of AZD9592: Half-life	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
Secondary	Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA)	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