A Phase III, Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy

A Phase III, Multicenter, Randomized, Open-Label, Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy

This study aims to Active-Controlled Study of SHR-A1811 Versus Trastuzumab Emtansine (T-DM1) in HER2-Positive Primary Breast Cancer Participants with Residual Invasive Disease Following Neoadjuvant Therapy，This study will examine SHR-A1811versus trastuzumab emtansine (T-DM1) in patients with HER2-positive primary breast cancer who have residual invasive disease in breast or axillary lymph nodes after neoadjuvant therapy.The primary objective is to compare invasive disease-free survival (IDFS) between SHR-A1811 and T-DM1 treatment arms in this population. The key secondary objective of the study is to evaluate disease-free survival (DFS), overall survival (OS) and distant recurrence-free interval (DRFI).

Study Overview

• Status: Recruiting
• Conditions: HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy
• Intervention / Treatment: Drug: SHR-A1811; Drug: Trastuzumab Emtansine

• Study Type: Interventional
• Enrollment (Estimated): 1600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ZhiYe Chen; Phone Number: +0518-81220121; Email: zhiye.chen.zc78@hengrui.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Principal Investigator: Jiong Wu
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
      • Principal Investigator: Jihui Hao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The age is 18-75 years old (including both ends), and female
2. HER2 positive invasive breast cancer Confirmed by pathological examination
3. Clinical Stage before Neoadjuvant Therapy was T1-4, N0-3, M0 (excluding T1N0).

4. Residual invasive cancer confirmed by pathological examination after radical surgery must meet one of the following two conditions:

   • If the clinical stage before neoadjuvant therapy is cT4N0-3M0 or cT1-3N2-3M0, there is residual invasive cancer in the primary breast lesion and/or ipsilateral axillary lymph nodes after surgery.
   • If the clinical stage before neoadjuvant therapy was cT1-3N0-1M0 (except T1N0), there was residual invasive cancer in the ipsilateral axillary lymph nodes after surgery.

5. Previous neoadjuvant therapy must meet all of the following conditions:

   • Neoadjuvant chemotherapy: At least 6 treatment cycles, including no less than 9 weeks of taxane-based chemotherapy (anthracycline-containing chemotherapy allowed).
   • Neoadjuvant anti-HER2 targeted therapy: No less than 9 weeks of targeted therapy including trastuzumab must be completed.
6. Have received radical surgery for breast cancer:
7. The interval from the completion of radical surgery to the first random medication should be at least 3 weeks and no more than 12 weeks.
8. Hormone receptor (HR) status was confirmed by postoperative pathologic examination. HR positive is defined as positive for the estrogen receptor (ER) or progesterone receptor (PR), and HR negative is defined as negative for both ER and PR.
9. The ECOG score is 0 or 1
10. Heart function is good
11. Agree to birth control

Exclusion Criteria:

1. Stage IV metastatic breast cancer
2. Evidence of recurrent breast cancer, including local recurrence, regional recurrence and distant metastasis .
3. In the past 5 years, patients suffered from other malignant tumors, excluding cured basal cell carcinoma of skin andcervical carcinoma in situ,.
4. Previously received systemic anti-HER2-ADC drug therapy, including but not limited to trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-DXd), etc.

5. Previous dosage requirements for anthracycline exposure meet one of the following conditions:

   • Doxorubicin or anthracyclines with similar exposure equivalent > 240mg/m2;
   • Epirubicin or liposomal doxorubicin hydrochloride > 480mg/m2.
6. History of cardiovascular diseases with clinical significance, such as severe/unstable angina pectoris, symptomatic congestive heart failure (NYHA ≥ Ⅱ), supraventricular or ventricular arrhythmia with clinical significance and requiring treatment or intervention, and myocardial infarction within 6 months.
7. Subjects with known or suspected interstitial pneumonia.
8. Known hereditary or acquired bleeding and thrombosis tendency.
9. History of active hepatitis B, hepatitis C or liver cirrhosis.
10. There were other serious physical or mental diseases or abnormal laboratory examinations that may increase the risk of participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811	Drug: SHR-A1811; Lyophilized powder injection, 100mg / bottle, intravenous drip
Active Comparator: Trastuzumab Emtansine (T-DM1)	Drug: Trastuzumab Emtansine; Lyophilized powder injection, 160mg / bottle, 100mg / bottle, intravenous drip

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Invasive disease-free survival (IDFS)	Randomization until the disease progressed, up to approximately 77 months postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease-free survival (DFS)	Randomization until the disease progressed, up to approximately 77 months postdose
Overall survival(OS)	Randomization until death from any cause, up to approximately 101 months postdose.
Distant recurrence-free interval (DRFI)	Randomization until distant recurrence or death from any cause, up to approximately 101 months postdose.
Safety endpointPercentage of Adverse Events in Participants	Baseline up to approximately 101 months postdose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2023
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Immunotoxins; Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
• Other Study ID Numbers: SHR-A1811-305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No