Endometrial Cancer, Malignant Solid Tumour
Conditions
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
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.
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.
Interventions
DRUGPuxitatug Samrotecan
2.4 mg/kg on Day 1 Q3W Route of administration: IV infusion
DRUGDoxorubicin
60 mg/m2 on Day 1 Q3W Route of administration: IV
DRUGPaclitaxel
80 mg/m2 on Days 1, 8, and 15 in 28-day cycle Route of Administration: IV
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Open label
Intervention model description
Single Open-Label
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) for Arm A vs Arm B | Approximately 3 years | PFS is defined as the time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause. |
| Overall survival (OS) for Arm A vs Arm B | Approximately 3 years | OS is defined as the time from randomization until the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Overall Response Rate (ORR) for Arm A vs Arm B | Approximately 3 years | 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. |
| Assessment of Duration of response (DoR) for Arm A vs Arm B | Approximately 3 years | 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. |
| Assessment of progression-free survival 2 (PFS2) for Arm A vs Arm B | Approximately 3 years | 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. |
| Time until first subsequent anticancer therapy after discontinuation of the randomized treatment, or death (TFST) for Arm A vs Arm B | Approximately 3 years | 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. |
| Time until the second subsequent anticancer therapy after discontinuation of the first subsequent treatment, or death (TSST) for Arm A vs Arm B | Approximately 3 years | 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. |
| Time until discontinuation of treatment for any reason, or death (TDT) for Arm A vs Arm B | Approximately 3 years | TDT is defined as the time from randomization until discontinuation of treatment for any reason, including disease progression, toxicity, and death. |
| Worsening in endometrial symptoms for Arm A vs Arm B | Approximately 3 years | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Japan, Lithuania, Netherlands, Poland, Singapore, Slovenia, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORBrian Slomovitz, MD
Icahn School of Medicine at Mount Sinai
PRINCIPAL_INVESTIGATORStephanie Gaillard, MD, PhD
Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center (SKCCC)
PRINCIPAL_INVESTIGATORNicole Concin, Prof.
Head of the Division of General Gynecology and Gynecologic Oncology at the Department of Obstetrics and Gynecology of MedUni Vienna and University
Outcome results
None listed