Clinical Trials/NCT05123482

NCT05123482RecruitingPhase 1

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)

AstraZeneca67 sites in 12 countries460 target enrollmentStarted: October 18, 2021Last updated: September 11, 2026

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Phase 1
Status: Recruiting
Sponsor: AstraZeneca
Enrollment: 460
Locations: 67
Primary Endpoint: The number of patients with adverse events

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

Brief 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

Detailed 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

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Sequential
Primary Purpose: Treatment
Masking: None

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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 bone marrow, hepatic, and renal function as defined in the protocol
•Additional Inclusion Criteria For Sub-Study 1 Part A:
•Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC or endometrial cancer
•Additional Inclusion Criteria For Sub-Study 1 Part B:
•Histologically or cytologically confirmed metastatic or locally advanced and recurrent disease for the respective cohort:
•Cohort B1 (Biliary Tract Cancer)
•Cohort B2 (Ovarian Cancer)
•Cohort B3 (Breast Cancer)
•Cohort B4 (Endometrial Cancer)
•Cohort B5 (Squamous Non-Small Cell Lung Cancer)
•Additional Inclusion Criteria 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, endometrial cancer or squamous non-small cell lung cancer.
•Additional Inclusion Criteria For Sub-Study 3 Part A:
•Minimum body weight ≥ 30 kg (for participants enrolled in cohorts including rilvegostomig only).
•Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, ovarian cancer, BTC, endometrial cancer or squamous non-small cell lung cancer.
•Additional Inclusion Criteria For Sub-Study 4 Part A:
•Minimum body weight ≥ 30 kg (for participants enrolled in cohorts including rilvegostomig only).
•Histologically or cytologically confirmed metastatic or locally advanced/recurrent breast cancer, endometrial cancer or squamous non-small cell lung cancer.
•Participants must have progressed following at least one but no more than 3 prior lines of treatment for metastatic or relapsed disease and have no satisfactory alternative treatment option as judged by the Investigator.

Exclusion Criteria

•Treatment with any of the following:
•Nitrosourea or mitomycin C within 6 weeks prior to the first dose of study treatment
•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
•Any other anticancer treatment within the following time periods prior to the first dose of study intervention:
•Cytotoxic treatment: 21 days
•Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter)
•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:
•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.
•Uncontrolled hypertension.
•Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months.
•History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
•Symptomatic heart failure (NYHA class ≥ 2).
•Prior or current cardiomyopathy.
•Severe valvular heart disease.
•Mean resting QTcF > 470 msec.
•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.
•Patients with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML (as determined by prior diagnostic investigation)
•Additional Exclusion Criteria For Sub-Study 2 Part A:
•Thromboembolic event within 3 months before the first dose of study intervention - No longer applicable per amendment 7
•Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
•Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
•History of organ transplant
•Additional Exclusion Criteria For Sub-Study 2 Part B
•Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.)
•Additional Exclusion Criteria For Sub-Study 3 Part A:
•Concomitant use of medications or herbal supplements known to be strong cytochrome P (CYP) 3A4 inducers/inhibitors.
•Any history of persisting (> 2 weeks) severe cytopenia due to any cause
•Patients with any known predisposition to bleeding
•Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib.
•Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.)
•Additional Exclusion Criteria For Sub-Study 4 Part A:
•Patients have received prior therapy with AZD9574 or more than 1 prior line of any other PARPi-based regimen
•Concomitant use of medications or herbal supplements known to be strong cytochrome P (CYP) 3A4 inducers/inhibitors.
•Previous treatment with rilvegostomig for the cohort treated with rilvegostomig
•Previous treatment with any therapy that contains a TOP1i (eg. irinotecan, topotecan, trastuzumab deruxtecan, etc.)
•Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574

Arms & Interventions

Sub-Study 1 AZD8205 Monotherapy

Experimental

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.

Intervention: AZD8205 (Drug)

Sub-Study 4: AZD8205 in combination with AZD9574 with or without rilvegostomig (AZD2936)

Experimental

Sub-Study 4 has two parts:

Part A : Dose escalation to determine the safety, tolerability of AZD8205 + AZD9574. Rilvegostomig may be added in a triplet combination once an AZD8205 + AZD9574 combination dose/schedule has been considered safe.

Part B: may be added in the future depending on emerging data, following a formal protocol amendment.

Intervention: AZD8205 in combination with AZD9574 (Drug)

Sub Study 2: AZD8205 in combination with rilvegostomig

Experimental

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.

Intervention: AZD8205 and AZD2936 (Rilvegostomig) (Drug)

Sub-Study 3 AZD8205 in combination with saruparib, with or without rilvegostomig

Experimental

Sub-Study 3 has two parts:

Part A : Dose escalation to determine the safety, tolerability of AZD8205 + saruparib. Rilvegostomig may be added in a triplet combination once an AZD8205 + saruparib combination dose/schedule has been considered safe.

Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + saruparib with or without rilvegostomig in select solid tumors.

Intervention: AZD8205 and AZD5305 (saruparib) (Drug)

Sub-Study 4: AZD8205 in combination with AZD9574 with or without rilvegostomig (AZD2936)

Experimental

Sub-Study 4 has two parts:

Part B: may be added in the future depending on emerging data, following a formal protocol amendment.

Intervention: AZD8205 in combination with AZD9574 plus rilvegostomig (AZD2936) (Drug)

Sub-Study 3 AZD8205 in combination with saruparib, with or without rilvegostomig

Experimental

Sub-Study 3 has two parts:

Part B: Dose expansion to evaluate anti-tumor activity of AZD8205 + saruparib with or without rilvegostomig in select solid tumors.

Intervention: AZD8205 and AZD5305 (saruparib) and AZD2936 (rilvegostomig) (Drug)

Outcomes

Primary Outcomes

The number of patients with adverse events

Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year).

Number of patients with adverse events by system organ class and preferred term

The number of patients with serious adverse events

Time Frame: From time of Informed consent to 30 days post last dose (approximately 1 year)

Number of patients with serious adverse events by system organ class and preferred term

The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.

Time Frame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days).

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.

The number of patients with changes from baseline laboratory findings, ECGs and vital signs

Time Frame: From time of informed consent to 30 days post last dose (approximately 1 year)

Description of laboratory findings and vital signs variables over time including change from baseline.

Secondary Outcomes

Objective Response Rate (ORR)(From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ))
Duration of response (DoR)(From the first documented response to confirmed progressive disease or death ( approx. 2 years ))
Progression free Survival (PFS)(From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ))
Disease Control Rate at 12 weeks (DCR-12)(Measured from first dose until progression. For each patient, this is expected to be at 12 weeks)
Overall Survival (OS)(From first dose of AZD8205 to death ( approx. 2 years ))
Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Clearance(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Immunogenicity of AZD8205.(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub Study 1: AZD8205 monotherapy Pharmacodynamics(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub Study 2: AZD8205 in combination with rilvegostomig Pharmacodynamics(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub-study 2: Rilvegostomig Pharmacokinetics when in combination with AZD8205(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-study 2: Immunogenicity of Rilvegostomig when in combination with AZD8205(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 3: Pharmacokinetics of saruparib in combination with AZD8205 with or without rilvegostomig(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-study 3: Pharmacokinetics of rilvegostomig in combination with AZD8205 and saruparib(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 3: Immunogenicity of rilvegostomig in combination with AZD8205 and saruparib(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Pharmacokinetics of AZD8205: Time to maximum plasma concentration of the study drug (T-max)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Terminal elimination half-life (t 1/2)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Objective Response Rate (ORR)(From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ))
Duration of response (DoR)(From the first documented response to confirmed progressive disease or death ( approx. 2 years ))
Immunogenicity of AZD8205.(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub-study 2: Immunogenicity of Rilvegostomig when in combination with AZD8205(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 4: Immunogenicity of rilvegostomig in combination with AZD8205 and AZD9574(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Progression free Survival (PFS)(From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years ))
Disease Control Rate at 12 weeks (DCR-12)(Measured from first dose until progression. For each patient, this is expected to be at 12 weeks)
Overall Survival (OS)(From first dose of AZD8205 to death ( approx. 2 years ))
Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Maximum plasma concentration of the study drug (Cmax)(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Pharmacokinetics of AZD8205: Clearance(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub Study 1: AZD8205 monotherapy Pharmacodynamics(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub-study 2: Rilvegostomig Pharmacokinetics when in combination with AZD8205(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 3: Pharmacokinetics of saruparib in combination with AZD8205 with or without rilvegostomig(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 4: Pharmacokinetics of AZD9574 in combination with AZD8205 with or without rilvegostomig(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub Study 2: AZD8205 in combination with rilvegostomig Pharmacodynamics(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years ))
Sub-study 3: Pharmacokinetics of rilvegostomig in combination with AZD8205 and saruparib(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-Study 3: Immunogenicity of rilvegostomig in combination with AZD8205 and saruparib(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))
Sub-study 4: Pharmacokinetics of rilvegostomig in combination with AZD8205 and AZD9574(From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years))

Investigators

Sponsor

AstraZeneca

Sponsor Class

Industry

Responsible Party

Sponsor

Study Sites (67)

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