A Phase I/IIa Study of AZD8205 Given Alone or in Combination With Anticancer Drugs, in Participants With Advanced or Metastatic Solid Malignancies

Breast Cancer Clinical Trial

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05123482
• Other study ID #: D6900C00001
• Secondary ID: 2021-000736-66
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 18, 2021
• Est. completion date: December 30, 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 research study is studying a new compound, AZD8205, as a possible treatment for advanced or metastatic solid tumours alone or in combination with anti-cancer agents

Description:

This study is 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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.

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.

Related Conditions & MeSH terms

• Biliary Tract Carcinoma
• Breast Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Ovarian Cancer

Intervention

Drug:
• 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
• 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.

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Melbourne
Australia	Research Site	Nedlands
Australia	Research Site	South Brisbane
Belgium	Research Site	Anderlecht
Belgium	Research Site	Leuven
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Kunming
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Italy	Research Site	Milan
Italy	Research Site	Modena
Italy	Research Site	Roma
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku
Japan	Research Site	Sunto-gun
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Amsterdam
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Pamplona
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
Thailand	Research Site	Bangkok
Thailand	Research Site	Chiang Mai
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	London
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Commack	New York
United States	Research Site	Duarte	California
United States	Research Site	Houston	Texas
United States	Research Site	Irvine	California
United States	Research Site	New York	New York
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Santa Monica	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Sarasota	Florida
United States	Research Site	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients with adverse events	Number of patients with adverse events by system organ class and preferred term	From time of Informed consent to 30 days post last dose (approximately 1 year).
Primary	The number of patients with serious adverse events	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 (approximately 1 year)
Primary	The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.	A DLT is defined as any toxicity that occurs from the first dose of study treatment up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation and which includes pre-defined haematological and non-haematological toxicities.	From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
Primary	The number of patients with changes from baseline laboratory findings, ECGs and vital signs	Description of laboratory findings and vital signs variables over time including change from baseline.	From time of informed consent to 30 days post last dose (approximately 1 year)
Secondary	Objective Response Rate (ORR)	The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1).	From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Secondary	Duration of response (DoR)	The time from the date of first response until date of disease progression (RECIST 1.1) or death in the absence of disease progression.	From the first documented response to confirmed progressive disease or death ( approx. 2 years )
Secondary	Progression free Survival (PFS)	The time from first dose until RECIST 1.1 defined disease progression or cessation of study treatment.	From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Secondary	Disease Control Rate at 12 weeks (DCR-12)	Percentage of patients with confirmed CR or PR or having SD maintained for >= 11 weeks from first dose (RECIST 1.1).	Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
Secondary	Overall Survival (OS)	The time from the date of the first dose of study treatment until death due to any cause.	From first dose of AZD8205 to death ( approx. 2 years )
Secondary	Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)	Area under the plasma concentration-time curve	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)	Maximum observed plasma concentration of the study drug	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)	Time to maximum observed plasma concentration of the study drug	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Pharmacokinetics of AZD8205: Clearance	A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)	Terminal elimination half life.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Immunogenicity of AZD8205.	The number and percentage of participants who develop ADAs.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Sub Study 1: AZD8205 monotherapy Pharmacodynamics	To assess the intratumoral pharmacodynamic biomarkers (gamma H2AX H-scores) to AZD8205 when administered as a monotherapy.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Secondary	Sub Study 2: AZD8205 in combination with AZD2936 Pharmacodynamics	To assess the change in intratumoral pharmacodynamic biomarkers (gamma H2AX H-scores) to AZD8205 when administered in combination with rilvegostomig.	From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )