Brief Summary
This is a Phase III, 2-arm, randomized, open label, multicenter, global study assessing the efficacy and safety of puxitatug samrotecan compared to physician's choice of chemotherapy (doxorubicin or paclitaxel) in participants with B7-H4 selected advanced/metastatic EC that progressed following platinum based chemotherapy and anti-PD-1/anti-PD-L1 therapy.
Brief Title
Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01)
Detailed Description
The target population of interest in this study is participants with B7-H4-selected advanced/metastatic EC who have progressed on or after platinum-based chemotherapy and anti-PD-1/anti-PD-L1 therapy, either separately or in combination and should have received no more than 2 prior lines of therapy in advanced/metastatic setting. Participants will be randomized in a 1:1 ratio to Puxi-Sam (arm A) or physician's choice of chemotherapy (arm B; doxorubicin or paclitaxel). The total study size will be approximately 700 eligible participants.
During the treatment period, participants will receive Puxi-Sam IV Day 1 Q3W (Arm A) or either doxorubicin treatment IV Day 1 Q3W or paclitaxel treatment IV on Days 1, 8, and 15 in 28-day cycle (Arm B).
This study aims to see if Puxi-Sam allows participants to live longer without their endometrial cancer getting worse, or simply to live longer, compared to participants receiving standard of care chemotherapy. This study is also looking to see how the treatment and the endometrial cancer affects participants' quality of life.
During the treatment period, participants will receive Puxi-Sam IV Day 1 Q3W (Arm A) or either doxorubicin treatment IV Day 1 Q3W or paclitaxel treatment IV on Days 1, 8, and 15 in 28-day cycle (Arm B).
This study aims to see if Puxi-Sam allows participants to live longer without their endometrial cancer getting worse, or simply to live longer, compared to participants receiving standard of care chemotherapy. This study is also looking to see how the treatment and the endometrial cancer affects participants' quality of life.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-877-240-9479
Central Contact Email
information.center@astrazeneca.com
Completion Date
Completion Date Type
Estimated
Conditions
Endometrial Cancer
Malignant Solid Tumour
Eligibility Criteria
The main inclusion criteria include but are not limited to the following:
* Histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
* Recurrent/metastatic EC ie, with radiological or objective evidence of recurrence or progression.
* Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.
* A WHO/ECOG performance status of 0 or 1 at Screening.
* Has radiographically measurable disease by RECIST 1.1
The main exclusion criteria include but are not limited to the following:
* Had uterine sarcomas or uterine neuroendocrine carcinoma.
* Has had a recurrence of endometrial carcinoma or carcinosarcoma more than \> 12 months after completing platinum-based therapy administered in the curative-intent setting without any additional platinum-based therapy received in the recurrent setting.
* Had previously received treatment with any therapy (approved or investigational) that contained a TOP1i including ADCs .
* Had previously received treatment with Puxi-Sam or another B7-H4 targeting agent.
* 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.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
* Active or previously documented autoimmune or inflammatory disorders
* Histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
* Recurrent/metastatic EC ie, with radiological or objective evidence of recurrence or progression.
* Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.
* A WHO/ECOG performance status of 0 or 1 at Screening.
* Has radiographically measurable disease by RECIST 1.1
The main exclusion criteria include but are not limited to the following:
* Had uterine sarcomas or uterine neuroendocrine carcinoma.
* Has had a recurrence of endometrial carcinoma or carcinosarcoma more than \> 12 months after completing platinum-based therapy administered in the curative-intent setting without any additional platinum-based therapy received in the recurrent setting.
* Had previously received treatment with any therapy (approved or investigational) that contained a TOP1i including ADCs .
* Had previously received treatment with Puxi-Sam or another B7-H4 targeting agent.
* 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.
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
* Active or previously documented autoimmune or inflammatory disorders
Inclusion Criteria
inclusion criteria include but are not limited to the following:
* Histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
* Recurrent/metastatic EC ie, with radiological or objective evidence of recurrence or progression.
* Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.
* A WHO/ECOG performance status of 0 or 1 at Screening.
* Has radiographically measurable disease by RECIST 1.1
The
* Histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
* Recurrent/metastatic EC ie, with radiological or objective evidence of recurrence or progression.
* Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.
* A WHO/ECOG performance status of 0 or 1 at Screening.
* Has radiographically measurable disease by RECIST 1.1
The
Gender
Female
Gender Based
false
Keywords
Bluestar-Endometrial01
AZD8205
Puxitatug Samrotecan
Puxi-Sam
Platinum-based chemotherapy
B7-H4
advanced/metastatic
Endometrial Cancer
Anti-PD-1
Anti-PD-L1
antibody-drug conjugate
Topoisomerase 1 Inhibitors
uterine neoplasm
female urogenital neoplasm
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07044336
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D6900C00003
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4 Selected Advanced/Metastatic Endometrial Cancer Who Progressed On or After Platinum Based Chemotherapy and Anti-PD-1/Anti-PD-L1 Therapy (Bluestar-Endometrial01)
Primary Outcomes
Outcome Description
PFS is defined as the time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause.
Outcome Measure
Progression Free Survival (PFS) for Arm A vs Arm B
Outcome Time Frame
Approximately 3 years
Outcome Description
OS is defined as the time from randomization until the date of death due to any cause.
Outcome Measure
Overall survival (OS) for Arm A vs Arm B
Outcome Time Frame
Approximately 3 years
Secondary Ids
Secondary Id
GOG-3110
Secondary Id
ENGOT-en28
Secondary Outcomes
Outcome Description
ORR is defined as the proportion of participants who have a response of CR or PR, as determined by BICR assessments, per RECIST 1.1.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Assessment of Overall Response Rate (ORR) for Arm A vs Arm B
Outcome Description
DoR will be defined as the time from the date of first documented response until the date of documented progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Assessment of Duration of response (DoR) for Arm A vs Arm B
Outcome Description
PFS2 will be defined as the time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after first subsequent therapy, or death.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Assessment of progression-free survival 2 (PFS2) for Arm A vs Arm B
Outcome Description
TFST is defined as the time from randomization until the start date of the first subsequent anticancer therapy after discontinuation of the randomized treatment, or death due to any cause.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Time until first subsequent anticancer therapy after discontinuation of the randomized treatment, or death (TFST) for Arm A vs Arm B
Outcome Description
TSST is defined as the time from randomization until the start date of the second subsequent anticancer therapy after discontinuation of the first subsequent treatment, or death due to any cause.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Time until the second subsequent anticancer therapy after discontinuation of the first subsequent treatment, or death (TSST) for Arm A vs Arm B
Outcome Description
TDT is defined as the time from randomization until discontinuation of treatment for any reason, including disease progression, toxicity, and death.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Time until discontinuation of treatment for any reason, or death (TDT) for Arm A vs Arm B
Outcome Description
Time to worsening is defined as time from date of randomization to the date of worsening while on treatment for endometrial symptoms, physical functioning, and health-related quality of life based on select items from the EORTC IL389.
Outcome Time Frame
Approximately 3 years
Outcome Measure
Worsening in endometrial symptoms for Arm A vs Arm B
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nicole Nevadunsky
Investigator Email
nnevadun@montefiore.org
Investigator Phone
718-405-8082
Investigator Department
Obstetrics & Gynecology and Womens Health
Investigator Division
Gynecological Oncology
Investigator Sponsor Organization
External
Study Department
Obstetrics & Gynecology and Women`s Health
Study Division
Gynecologic Oncology
Categories Mesh Debug
Gynecologic Cancers --- GENITAL NEOPLASMS, FEMALE
Genitourinary (GU) & Urologic Cancers --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
MeSH Terms
ENDOMETRIAL NEOPLASMS
NEOPLASM METASTASIS
UTERINE NEOPLASMS
GENITAL NEOPLASMS, FEMALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
UTERINE DISEASES
GENITAL DISEASES, FEMALE
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
GENITAL DISEASES
NEOPLASTIC PROCESSES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
DOXORUBICIN
PACLITAXEL
DAUNORUBICIN
ANTHRACYCLINES
NAPHTHACENES
POLYCYCLIC AROMATIC HYDROCARBONS
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
POLYCYCLIC COMPOUNDS
AMINOGLYCOSIDES
GLYCOSIDES
CARBOHYDRATES
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
DITERPENES
TERPENES