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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05647122




Registration number
NCT05647122
Ethics application status
Date submitted
18/11/2022
Date registered
12/12/2022

Titles & IDs
Public title
First in Human Study of AZD9592 in Solid Tumors
Scientific 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
Secondary ID [1] 0 0
D9350C00001
Universal Trial Number (UTN)
Trial acronym
EGRET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 0 0
Carcinoma Non-small Cell Lung 0 0
Head and Neck Neoplasms 0 0
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD9592
Treatment: Drugs - Osimertinib
Treatment: Drugs - 5-Fluorouracil (5-FU)
Treatment: Drugs - Leucovorin
Treatment: Drugs - Bevacizumab

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

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

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)


Treatment: Drugs: AZD9592
Varying doses of AZD9592

Treatment: Drugs: Osimertinib
tablets administered orally

Treatment: Drugs: 5-Fluorouracil (5-FU)
IV infusion

Treatment: Drugs: Leucovorin
IV infusion

Treatment: Drugs: Bevacizumab
IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs)
Timepoint [1] 0 0
From time of Informed Consent to 30 days post last dose of AZD9592
Primary outcome [2] 0 0
Incidence of Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From time of Informed Consent to 30 days post last dose of AZD9592
Primary outcome [3] 0 0
Incidence of dose-limiting toxicities (DLT) as defined in the protocol
Timepoint [3] 0 0
From time of first dose of AZD9592 to end of DLT period (approximately 21 days)
Primary outcome [4] 0 0
Incidence of baseline laboratory finding, ECG and vital signs changes
Timepoint [4] 0 0
From time of Informed Consent to 30 days post last dose of AZD9592
Primary outcome [5] 0 0
Proportion of patients with radiological response (ORR)
Timepoint [5] 0 0
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
Secondary outcome [2] 0 0
Duration of Response (DoR)
Timepoint [2] 0 0
From date of first dose of AZD9592 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
Secondary outcome [3] 0 0
Disease Control Rate (DCR) at 12 weeks
Timepoint [3] 0 0
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 outcome [4] 0 0
Progression free Survival (PFS)
Timepoint [4] 0 0
From date of first dose of AZD9592 up until date of progression or death due to any cause (approximately 2 years)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From date of first dose of AZD9592 up until the date of death due to any cause (approximately 2 years)
Secondary outcome [6] 0 0
Pharmacokinetics of AZD9592: Plasma PK concentrations
Timepoint [6] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [7] 0 0
Pharmacokinetics of AZD9592: Area under the concentration time curve (AUC)
Timepoint [7] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [8] 0 0
Pharmacokinetics of AZD9592: Maximum plasma concentration of the study drug (C-max)
Timepoint [8] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [9] 0 0
Pharmacokinetics of AZD9592: Time to maximum plasma concentration of the study drug (T-max)
Timepoint [9] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [10] 0 0
Pharmacokinetics of AZD9592: Clearance
Timepoint [10] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [11] 0 0
Pharmacokinetics of AZD9592: Half-life
Timepoint [11] 0 0
From date of first dose of AZD9592 up until 30 days post last dose
Secondary outcome [12] 0 0
Immunogenicity of AZD9592: Anti-Drug Antibodies (ADA)
Timepoint [12] 0 0
From date of first dose of AZD9592 up until 30 days post last dose

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/12/2025
Actual
Sample size
Target
162
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Kogarah
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Rhode Island
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
China
State/province [14] 0 0
Beijing
Country [15] 0 0
China
State/province [15] 0 0
Chongqing
Country [16] 0 0
China
State/province [16] 0 0
Guangzhou
Country [17] 0 0
China
State/province [17] 0 0
Harbin
Country [18] 0 0
China
State/province [18] 0 0
Wuhan
Country [19] 0 0
France
State/province [19] 0 0
Rennes
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Orbassano
Country [23] 0 0
Italy
State/province [23] 0 0
Rozzano
Country [24] 0 0
Italy
State/province [24] 0 0
Verona
Country [25] 0 0
Japan
State/province [25] 0 0
Chuo-ku
Country [26] 0 0
Japan
State/province [26] 0 0
Kashiwa
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Malaysia
State/province [28] 0 0
Kuala Lumpur
Country [29] 0 0
Malaysia
State/province [29] 0 0
Kuching
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Sevilla
Country [33] 0 0
Taiwan
State/province [33] 0 0
Taichung
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei City
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Charu Aggarwal, MD, MPH
Address 0 0
University of Pennsylvania
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05647122