A Study of T-DXd in AI-Assessed HER2-Ultralow Metastatic Breast Cancer

NCT07782086 | Not Yet Recruiting

• 1 other identifier: D9673L00026
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 14

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; HER2-ultralow; Trastuzumab Deruxtecan; T-DXd; AI-assisted Pathology; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  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.

  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.

Secondary Outcomes (3)

• 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.

• 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 .

• 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 .

Other Outcomes (3)

• Safety Objective

  From ICF signing through 40 days post-last dose or until subsequent therapy, up to approximate 36 months following subject enrolment .

• OS

  From first dose to death, assessed every 3 months during LTFU, up to approximate 36 months following subject enrolment .

• Al-assisted Re-scoring Data

  Tissue screening period prior to screening.

Study Arms (1)

Trastuzumab Deruxtecan (T-DXd) Treatment Arm

EXPERIMENTAL

Single-arm treatment group: All participants will receive trastuzumab deruxtecan (T-DXd) 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal.

Drug: Trastuzumab Deruxtecan (T-DXd, ENHERTU®)

Interventions

Trastuzumab Deruxtecan (T-DXd, ENHERTU®) DRUG

5.4 mg/kg IV infusion every 3 weeks (Q3W)

Trastuzumab Deruxtecan (T-DXd) Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of ICF prior to any study-specific qualification procedures.
• Adults ≥ 18 years of age at the time the ICF is signed.
• 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.
• Pathologically documented BC that:
• Is unresectable and/or metastatic.
• 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.
• Has a history of HER2 IHC 0 (with/without membrane staining).
• Was never previously reported as HER2+ (IHC 3+ or ISH+) as per ASCO CAP guidelines.
• 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.
• Must have progressed on at least one and up to two prior lines of ET ± targeted therapy in the metastatic setting.
• 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.
• 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.
• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Has a minimum life expectancy of 12 weeks at Screening.
• Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before enrollment.

You may not qualify if:

• Subjects with contraindications to T-DXd per the local prescribing information and T-DXd IB cannot be enrolled to the study.
• Previous treatment with anti-HER2 therapy.
• Prior treatment with an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
• Subjects with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval by Fredericia's method (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG).
• 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.
• Lung criteria:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disorder \[COPD\], restrictive lung disease, pleural effusion, etc.).
• Any autoimmune, connective tissue or inflammatory disorders (including Rheumatoid arthritis, Sjogren's and sarcoidosis) where there is documented, or a suspicion of pulmonary involvement at the time of Screening.
• Prior pneumonectomy (complete).
• Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals.
• Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B (hepatitis B virus surface antigen \[HBsAg\] or hepatitis B virus core antibody \[HBcAb\] positive, at Screening) or C virus infection. Subjects should be tested for HIV prior to enrollment if required by local regulations or institutional review board (IRB)/ethics committee (EC). Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA). Subjects with past or resolved hepatitis B virus (HBV) infection are eligible only if they meet all of the following criteria:
• HBsAg (-) (for \> 6 months off anti-viral treatment).

Sponsors & Collaborators

• Shuangyue Liu: lead

Study Sites (14)

The Second Affiliated Hospital Of Anhui Medical University

Hefei, Anhui, China

Location

Peking University Of Third Hospital

Beijing, Beijing Municipality, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Location

Affiliated Zhongshan Hospital Of Dalian University

Dalian, Liaoning, China

Location

Changhai Hospital

Shanghai, Shanghai Municipality, China

Location

Tongji Hospital Tongji University

Shanghai, Shanghai Municipality, China

Location

Xijing Hospital, Air Force Medical University

Xi’an, Shanxi, China

Location

Sichuan Cancer Hospital

Chengdu, Sichuan, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

The Affiliated Hospital Of Southwest Medical University

Luzhou, Sichuan, China

Location

Zigong First People's Hospital

Zigong, Sichuan, China

Location

Tianjing Cancer Hospital Airport Hospital

Tianjin, Tianjin Municipality, China

Location

The 1st Affiliated Hospital of WMU

Wenzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Haomiao Lan

  Zigong No.1 Peoples Hospital

  PRINCIPAL INVESTIGATOR

• Ting Wang

  The First Affiliated Hospital of Air Force Medicial University

  PRINCIPAL INVESTIGATOR

• Lijia He

  The Affiliated Hospital Of Southwest Medical University

  PRINCIPAL INVESTIGATOR

• Hao Wang

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

• Xuening Ji

  Affiliated Zhongshan Hospital of Dalian University

  PRINCIPAL INVESTIGATOR

• Xiaoxiao Liu

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Fanfan Li

  The Second Hospital of Anhui Medical University

  PRINCIPAL INVESTIGATOR

• Mopei Wang

  Peking University Of Third Hospital

  PRINCIPAL INVESTIGATOR

• Fengfeng Cai

  Tongji Hospital Tongji University

  PRINCIPAL INVESTIGATOR

• Wei Li

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

• Ouchen Wang

  The 1st Affiliated Hospital of WMU

  PRINCIPAL INVESTIGATOR

• Hengyu Li

  Changhai Hospital

  PRINCIPAL INVESTIGATOR

• Chunfang Hao

  Tianjing Cancer Hospital Airport Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ping zhang

CONTACT

028-85422953; zheng.zd@wchscu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Breast Disease Center

Model Details: 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.

Study Record Dates

• First Submitted: July 6, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): September 7, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (14)