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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05123482




Registration number
NCT05123482
Ethics application status
Date submitted
13/10/2021
Date registered
17/11/2021

Titles & IDs
Public title
A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies
Scientific title
A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (BLUESTAR)
Secondary ID [1] 0 0
2021-000736-66
Secondary ID [2] 0 0
D6900C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Biliary Tract Carcinoma 0 0
Ovarian Cancer 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD8205
Treatment: Drugs - AZD8205 and AZD2936 (Rilvegostomig)

Experimental: Sub-Study 1 AZD8205 Monotherapy - Sub-Study 1 has two parts:

Part A : The aim is to determine the safety, tolerability, Recommended Phase 2 Dose(RP2D), and/or the Maximum Tolerated Dose (MTD) of AZD8205.

Part B: The aim of dose expansion is to evaluate anti-tumor activity of AZD8205 as monotherapy in select solid tumors.

Experimental: Sub Study 2: AZD8205 in combination with rilvegostomig - Sub-Study 2 has two parts:

Part A : Dose escalation to determine the safety, tolerability of AZD8205 + rilvegostomig Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + rilvegostomig in select solid tumors.


Treatment: Drugs: AZD8205
AZD8205 is an antibody drug conjugate that has the potential to treat a wide variety of solid tumors including but not limited to breast cancer, Biliary Tract Cancer, ovarian, and endometrial cancers

Treatment: Drugs: AZD8205 and AZD2936 (Rilvegostomig)
AZD8205 is an antibody drug conjugate that has the potential to treat a wide variety of solid tumors including but not limited to breast cancer, Biliary Tract Cancer, ovarian, and endometrial cancers.

Rilvegostomig is a bispecific antibody that specifically binds to human TIGIT and PD-1 and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of patients with adverse events
Timepoint [1] 0 0
From time of Informed consent to 30 days post last dose (approximately 1 year).
Primary outcome [2] 0 0
The number of patients with serious adverse events
Timepoint [2] 0 0
From time of Informed consent to 30 days post last dose (approximately 1 year)
Primary outcome [3] 0 0
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
Timepoint [3] 0 0
From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
Primary outcome [4] 0 0
The number of patients with changes from baseline laboratory findings, ECGs and vital signs
Timepoint [4] 0 0
From time of informed consent to 30 days post last dose (approximately 1 year)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Secondary outcome [2] 0 0
Duration of response (DoR)
Timepoint [2] 0 0
From the first documented response to confirmed progressive disease or death ( approx. 2 years )
Secondary outcome [3] 0 0
Progression free Survival (PFS)
Timepoint [3] 0 0
From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Secondary outcome [4] 0 0
Disease Control Rate at 12 weeks (DCR-12)
Timepoint [4] 0 0
Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
From first dose of AZD8205 to death ( approx. 2 years )
Secondary outcome [6] 0 0
Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)
Timepoint [6] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [7] 0 0
Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)
Timepoint [7] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [8] 0 0
Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)
Timepoint [8] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [9] 0 0
Pharmacokinetics of AZD8205: Clearance
Timepoint [9] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [10] 0 0
Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)
Timepoint [10] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [11] 0 0
Immunogenicity of AZD8205.
Timepoint [11] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [12] 0 0
Sub Study 1: AZD8205 monotherapy Pharmacodynamics
Timepoint [12] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary outcome [13] 0 0
Sub Study 2: AZD8205 in combination with AZD2936 Pharmacodynamics
Timepoint [13] 0 0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )

Eligibility
Key inclusion criteria
Key

* Age = 18 years
* Relapsed/metastatic solid tumors treated with prior adequate standard of care therapy for tumor type and stage of disease or where in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy.
* Measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-1
* Life expectancy = 12 weeks
* Adequate organ and marrow function as defined in the protocol

For Sub-Study 1 Part A:

• Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer

For Sub-Study 1 Part B:

* Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort:

1. Cohort B1 (Biliary Tract Cancer)
2. Cohort B2 (Ovarian Cancer)
3. Cohort B3 (Breast Cancer)
4. Cohort B4 (Endometrial Cancer)

For Sub-Study 2 Part A:
* Minimum body weight = 30 kg.
* Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with any of the following:

1. Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment
2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study treatment
3. Any other anticancer treatment within the following time periods prior to the first dose of study intervention:

1. Cytotoxic treatment: 21 days
2. Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter)
3. Biological products including immuno-oncology agents: 28 days
* Spinal cord compression or a history of leptomeningeal carcinomatosis.
* Brain metastases unless treated, 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.
* Active infection including tuberculosis and HBV, HCV or HIV
* 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.
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Participants with any of the following cardiac criteria:

1. History of arrhythmia which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation, or asymptomatic sustained ventricular tachycardia.
2. Uncontrolled hypertension.
3. Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.
4. History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
5. Symptomatic heart failure (NYHA class = 2).
6. Prior or current cardiomyopathy.
7. Severe valvular heart disease.
8. Mean resting QTcF > 470 msec.
9. Risk factors for QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.

Additional Exclusion Criteria for Part A Sub study 2

1. Thromboembolic event within 3 months before the first dose of study intervention.
2. Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
3. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Other
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
18/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2025
Actual
Sample size
Target
340
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment hospital [4] 0 0
Research Site - South Brisbane
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
VIC 3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Belgium
State/province [12] 0 0
Anderlecht
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
China
State/province [18] 0 0
Beijing
Country [19] 0 0
China
State/province [19] 0 0
Changsha
Country [20] 0 0
China
State/province [20] 0 0
Chongqing
Country [21] 0 0
China
State/province [21] 0 0
Guangzhou
Country [22] 0 0
China
State/province [22] 0 0
Kunming
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Italy
State/province [24] 0 0
Milan
Country [25] 0 0
Italy
State/province [25] 0 0
Modena
Country [26] 0 0
Italy
State/province [26] 0 0
Roma
Country [27] 0 0
Italy
State/province [27] 0 0
Rozzano
Country [28] 0 0
Japan
State/province [28] 0 0
Chuo-ku
Country [29] 0 0
Japan
State/province [29] 0 0
Kashiwa
Country [30] 0 0
Japan
State/province [30] 0 0
Koto-ku
Country [31] 0 0
Japan
State/province [31] 0 0
Sunto-gun
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Netherlands
State/province [33] 0 0
Amsterdam
Country [34] 0 0
Poland
State/province [34] 0 0
Warszawa
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
L'Hospitalet de Llobregat
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Málaga
Country [39] 0 0
Spain
State/province [39] 0 0
Pamplona
Country [40] 0 0
Taiwan
State/province [40] 0 0
Tainan
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taipei
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taoyuan
Country [43] 0 0
Thailand
State/province [43] 0 0
Bangkok
Country [44] 0 0
Thailand
State/province [44] 0 0
Chiang Mai
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cambridge
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Cardiff
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London

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
Address 0 0
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
[email protected]
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/NCT05123482