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)
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
Arms & interventions
- DrugAZD8205
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, endometrial cancers and squamous non-small cell lung cancers.
- DrugAZD8205 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, endometrial cancers and squamous non-small cell lung 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.
- DrugAZD8205 and AZD5305 (saruparib)
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, endometrial and squamous non-small cell lung cancers. Saruparib is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.
- DrugAZD8205 and AZD5305 (saruparib) 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, endometrial and squamous non-small cell lung cancers. Saruparib is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors. 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.
- DrugAZD8205 in combination with AZD9574
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, endometrial and squamous non-small cell lung cancers. AZD9574 is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors.
- DrugAZD8205 in combination with AZD9574 plus rilvegostomig (AZD2936)
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, endometrial and squamous non-small cell lung cancers. AZD9574 is a PARP inhibitor that stops the PARP protein from doing its repair work in damaged cancer cells, resulting in cell death, and is a potential anticancer therapy in patients with advanced or metastatic solid tumors. 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.
Outcome measures
Primary
The number of patients with adverse events
Number of patients with adverse events by system organ class and preferred term
Time frame: From time of Informed consent to 30 days post last dose (approximately 1 year).
The number of patients with serious adverse events
Number of patients with serious adverse events by system organ class and preferred term
Time frame: From time of Informed consent to 30 days post last dose (approximately 1 year)
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.
Time frame: From first dose of study treatment until the end of Cycle 1 (approximately 21 days).
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.
Time frame: From time of informed consent to 30 days post last dose (approximately 1 year)
Secondary
Objective Response Rate (ORR)
Time frame: From first dose of AZD8205 to progressive disease or death in the absence of disease progression ( approx. 2 years )
Duration of response (DoR)
Time frame: From the first documented response to confirmed progressive disease or death ( approx. 2 years )
Progression free Survival (PFS)
Time frame: 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)
Time frame: Measured from first dose until progression. For each patient, this is expected to be at 12 weeks
Overall Survival (OS)
Time frame: From first dose of AZD8205 to death ( approx. 2 years )
Pharmacokinetics of AZD8205: Area Under the concentration-time curve (AUC)
Time frame: 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)
Time frame: 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)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Pharmacokinetics of AZD8205: Clearance
Time frame: 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)
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Immunogenicity of AZD8205.
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 ( approx 2 years )
Sub Study 1: AZD8205 monotherapy Pharmacodynamics
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From the first dose of study intervention, at predefined intervals throughout the administration of AZD8205 (approx 2 years)
Eligibility criteria
Study locations (14)
Research Site
Duarte, California, 91010
Research Site
Irvine, California, 92618
Research Site
Santa Monica, California, 90404
Research Site
Santa Rosa, California, 95403
Research Site
Shreveport, Louisiana, 71103
Research Site
Baltimore, Maryland, 21231
Research Site
Boston, Massachusetts, 02215
Research Site
St Louis, Missouri, 63110
Research Site
Albuquerque, New Mexico, 87109
Research Site
Commack, New York, 11725
Research Site
New York, New York, 10029
Research Site
Charlotte, North Carolina, 28204
Research Site
Pittsburgh, Pennsylvania, 15213
Research Site
Houston, Texas, 77030
References
- Huang Y, Tan HY, Yuan J, Mu R, Yang J, Ball K, Vijayakrishnan B, Masterson L, Kinneer K, Luheshi N, Liang M, Rosenbaum AI. Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability In Vivo. Anal Chem. 2024 Oct 22;96(42):16525-16533. doi: 10.1021/acs.analchem.4c02309. Epub 2024 Oct 11.(PubMed)