Comparing SHR-A1811 and T-DM1 for HER2-Positive Breast Cancer After 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 is testing whether a new treatment called SHR-A1811 works better than T-DM1 for people with HER2-positive breast cancer who still have signs of the disease after initial therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1600 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (Industry-sponsored)
• Drugs / interventions: trastuzumab, chemotherapy, Doxorubicin
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06126640 on ClinicalTrials.gov

What this trial studies

This clinical trial compares the effectiveness of SHR-A1811 and Trastuzumab Emtansine (T-DM1) in treating HER2-positive primary breast cancer patients who have residual invasive disease following neoadjuvant therapy. The primary goal is to assess invasive disease-free survival (IDFS) between the two treatment options. Secondary objectives include evaluating disease-free survival (DFS), overall survival (OS), and distant recurrence-free interval (DRFI). Participants will receive either SHR-A1811 or T-DM1 to determine which provides better outcomes.

Who should consider this trial

Good fit: Ideal candidates are females aged 18-75 with HER2-positive invasive breast cancer and residual invasive disease after neoadjuvant therapy.

Not a fit: Patients with non-HER2-positive breast cancer or those without residual invasive disease after neoadjuvant therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options and outcomes for patients with HER2-positive breast cancer.

How similar studies have performed: Other studies have shown promising results with similar approaches in treating HER2-positive breast cancer, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: ZhiYe Chen

Conditions HER2-Positive Primary Breast Cancer Participants With Residual Invasive Disease Following Neoadjuvant Therapy