Breast Cancer
Conditions
Keywords
Breast Cancer, HER2-ultralow, Trastuzumab Deruxtecan, T-DXd, AI-assisted Pathology, Metastatic Breast Cancer
Brief summary
This is a prospective, multicenter, single-arm study designed to verify the efficacy and safety of trastuzumab deruxtecan (T-DXd) in subjects with hormone receptor-positive (HR+) unresectable and/or metastatic breast cancer who are identified as HER2-ultralow by artificial intelligence (AI)-assisted re-scoring after being manually scored as HER2-null. Eligible subjects will have progressed on at least one and up to two prior lines of endocrine therapy in the metastatic setting. Subjects are permitted to have received no more than one prior chemotherapy in the metastatic setting; however, chemotherapy must not have been the most recent treatment regimen at disease progression. Approximately 30 subjects will be enrolled at about 15 sites in China. The primary endpoint is objective response rate (ORR) by investigator assessment per RECIST 1.1.
Detailed description
This is a prospective, multicenter, single-arm, open-label study. The study will consist of four periods: Tissue Screening, Screening, Treatment, and Follow-up (including long-term follow-up). Subjects will receive T-DXd 5.4 mg/kg via intravenous infusion on Day 1 of each 21-day cycle. Radiographic tumor assessments will be performed every 6 weeks for the first 24 weeks, and then every 12 weeks thereafter until investigator-assessed disease progression. The primary objective is to evaluate the efficacy as assessed by ORR. Secondary objectives include PFS, DCR, and DoR. Safety will be assessed by TEAEs, SAEs, AESIs, and laboratory findings. One interim analysis is planned at approximately 6 months after the last subject enrolled. The study is expected to enroll 30 subjects at approximately 15 sites in China. The End of Study is defined as the timepoint at which 20 PFS events have been observed, estimated to occur approximately 15 months after the last subject is enrolled.
Interventions
DRUGTrastuzumab Deruxtecan (T-DXd, ENHERTU®)
5.4 mg/kg IV infusion every 3 weeks (Q3W)
Sponsors
Shuangyue Liu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single-arm, open-label, Post marketl study. All eligible subjects will receive trastuzumab deruxtecan (T-DXd) at 5.4 mg/kg via intravenous infusion every 3 weeks (Q3W) until disease progression, unacceptable toxicity, or study withdrawal. No control group is included; all studys are assigned to the same treatment arm to evaluate the efficacy and safety of T-DXd in subjects7/6/2026 with manually scored HER2-null, AI re-scored HER2-ultralow (HER2UL) unresectable or metastatic breast cancer.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For inclusion in the study subjects should fulfil the following criteria based on local regulations: 1. Provision of ICF prior to any study-specific qualification procedures. 2. Adults ≥ 18 years of age at the time the ICF is signed. 3. Must have an adequate tumor tissue sample available for assessment of HER2 status obtained most recently at the time of metastatic disease or later. If a suitable archival sample is not available, a fresh biopsy sample may be used to determine eligibility. 4. Pathologically documented BC that: 1. Is unresectable and/or metastatic. 2. Is documented as HR+ (either estrogen receptor \[ER\] and/or progesterone receptor \[PR\] positive \[ER or PR ≥1%\]) per ASCO CAP guidelines32 in the metastatic setting. If a patient has had multiple ER/PR results after metastatic disease, the most recent test result will be used to confirm eligibility. 3. Has a history of HER2 IHC 0 (with/without membrane staining). 4. Was never previously reported as HER2+ (IHC 3+ or ISH+) as per ASCO CAP guidelines. 5. Is scored as HER2-null (IHC 0; no membrane staining) by a local laboratory using the PATHWAY/VENTANA® HER2 (4B5) assay, and subsequently re-scored as HER2-ultralow (IHC 0; with membrane staining) under AI assistance by the central laboratory based on the stained slides sent by local laboratory. 5. Must have progressed on at least one and up to two prior lines of ET ± targeted therapy in the metastatic setting. 6. Have received no more than one chemotherapy in the metastatic setting but chemotherapy must not be the most recent treatment for patients at disease progression. 7. Presence of at least one measurable lesion based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the Investigator, per RECIST version 1.1. 8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. 9. Has a minimum life expectancy of 12 weeks at Screening. 10. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before enrollment. 11. Adequate organ and bone marrow function within 14 days before enrolment.. All parameters must be the most recent results available. Note: Transfusion (red blood cell or platelet) or granulocyte colony-stimulating factor (G-CSF) administration is not allowed within 14 days prior to the day on which bone marrow function is assessed, or at any time after this day and prior to Cycle 1 Day 1 (C1D1). 12. Adequate treatment washout period before enrollment, 13. Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the Screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of study treatment.Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. 14. Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 4 from the time of Screening and must agree to continue using such precautions for 7 months after the last dose of study treatment. Not all methods of contraception are highly effective. It is strongly recommended that non-sterilized male partners of female subjects of childbearing potential use a male condom plus spermicide while on study and for 7 months after the last dose of study treatment (note: male condoms are not reliable as a sole contraception method). Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the subject's usual lifestyle (consideration must be made to the duration of the clinical study); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. 15. Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from Screening to 4 months after the final dose of study treatment. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the subject's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male subject to also use at least one highly effective method of contraception throughout this period, as described in Table 4. In addition, male subjects should refrain from fathering a child throughout the study Treatment Period and for 4 months after the last dose of study treatment. Male subjects should refrain from freezing or donating sperm from the time of first exposure until 4 months after the final dose of the study treatment. Preservation of sperm should be considered prior to enrollment in this study. 16. Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study Treatment Period, and for at least 7 months after the final study treatment administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.
Exclusion criteria
* Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | From first dose to progression/death, assessed every 6 weeks for 24 weeks, then every 12 weeks, up to approximate 36 months following subject enrolment. | ORR is defined as the percentage of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by Investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From first dose to progression/death, assessed every 6 weeks for 24 weeks, then every 12 weeks, up to approximate 36 months following subject enrolment. | PFS is defined as the time from first dose of study treatment until progression per RECIST 1.1 as assessed by Investigator, or death due to any cause in the absence of progression regardless of whether the subject withdraws from study treatment or received another anticancer therapy prior to progression. |
| DCR | From first dose to progression/death, assessed every 6 weeks for 24 weeks, then every 12 weeks, up to approximate 36 months following subject enrolment . | DCR is defined as the percentage of subjects who have a BOR of CR/PR/SD. |
| DoR | From confirmed response to progression/death, assessed every 6 weeks for 24 weeks, then every 12 weeks, up to approximate 36 months following subject enrolment . | DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression as assessed by the Investigator per RECIST 1.1 or death in the absence of disease progression. |
Countries
China
Contacts
CONTACTping zhang
PRINCIPAL_INVESTIGATORHaomiao Lan
Zigong No.1 Peoples Hospital
PRINCIPAL_INVESTIGATORTing Wang
The First Affiliated Hospital of Air Force Medicial University
PRINCIPAL_INVESTIGATORLijia He
The Affiliated Hospital Of Southwest Medical University
PRINCIPAL_INVESTIGATORHao Wang
Sichuan Cancer Hospital and Research Institute
PRINCIPAL_INVESTIGATORXuening Ji
Affiliated Zhongshan Hospital of Dalian University
PRINCIPAL_INVESTIGATORXiaoxiao Liu
The Affiliated Hospital of Xuzhou Medical University
PRINCIPAL_INVESTIGATORFanfan Li
The Second Hospital of Anhui Medical University
PRINCIPAL_INVESTIGATORMopei Wang
Peking University Of Third Hospital
PRINCIPAL_INVESTIGATORFengfeng Cai
Tongji Hospital Tongji University
PRINCIPAL_INVESTIGATORWei Li
The First Affiliated Hospital with Nanjing Medical University
PRINCIPAL_INVESTIGATOROuchen Wang
The 1st Affiliated Hospital of WMU
PRINCIPAL_INVESTIGATORHengyu Li
Changhai Hospital
PRINCIPAL_INVESTIGATORChunfang Hao
Tianjing Cancer Hospital Airport Hospital
Outcome results
None listed