Neoadjuvant trastuzumab rezetecan plus toripalimab for HR‑positive, HER2‑low breast cancer

A Prospective, Multigroup, Multi-center, Open-label Clinical Study of Trastuzumab Rezetecan as Neoadjuvant Therapy Combined With Toripalimab in HR+/HER2-low Breast Cancer Patients (NEOTORCH-BREAST 08)

This trial will test whether giving trastuzumab rezetecan with toripalimab before surgery helps people with HR‑positive/HER2‑low breast cancer shrink tumors and achieve complete responses.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 111 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: First Affiliated Hospital of Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, Trastuzumab, Toripalimab
• Locations: 5 sites (Harbin and 4 other locations)
• Trial ID: NCT07383818 on ClinicalTrials.gov

What this trial studies

This is a prospective, multi‑cohort, multicenter, open‑label Phase 2 trial of neoadjuvant trastuzumab rezetecan combined with toripalimab, with some cohorts receiving standard chemotherapy. The primary endpoint is pathologic complete response (pCR) and the trial will record the incidence and types of adverse events. Secondary endpoints include event‑free survival (EFS), residual cancer burden (RCB), and objective response rate (ORR). Eligible patients are adults with newly diagnosed, operable HR‑positive/HER2‑low breast cancer and no prior systemic anticancer therapy.

Who should consider this trial

Good fit: Ideal candidates are women aged 18–70 with newly diagnosed, operable HR‑positive/HER2‑low breast cancer (T1cN1‑2 or T2‑3N0‑2), ECOG 0–1, and no prior anti‑cancer treatment.

Not a fit: Patients with HER2‑zero or HER2‑positive tumors, metastatic disease, significant organ dysfunction, or contraindications to antibody‑drug conjugates or PD‑1 inhibitors are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could increase the number of patients who achieve a pathologic complete response before surgery and potentially improve long‑term outcomes.

How similar studies have performed: Other HER2‑targeting antibody‑drug conjugates (for example trastuzumab deruxtecan) have shown activity in HER2‑low breast cancer and combining ADCs with PD‑1 inhibitors is an emerging strategy that has shown promising but still early evidence.

Eligibility criteria

Inclusion Criteria:

1. Female patients aged 18-70 years old;
2. ECOG score is 0-1 points;
3. Histologically or pathologically confirmed invasive breast cancer, meeting the following criteria simultaneously: Invasive breast cancer staged as T1cN1-2M0 or T2-3N0-2M0; All patients must be pathohistologically confirmed as HR-positive/HER2-low. The interpretation of ER and PR status follows the 2020 ASCO/CAP Guidelines: expression ≥1% is defined as positive, and HR positivity is confirmed if either ER or PR is positive. The interpretation of HER2 status follows the 2023 ASCO/CAP Guidelines: HER2-low is defined as HER2 1+ or 2+ with negative FISH test results. Pathological testing for PD-L1 expression: The Combined Positive Score (CPS) is the percentage of PD-L1-positive cells (including tumor cells, lymphocytes, and macrophages) among the total number of tumor cells. The PD-L1 antibody clone used for detection at our center is 22C3. No prior anti-cancer treatment.
4. Function levels of major organs must meet the required criteria
5. For female patients who have not yet reached menopause or undergone surgical sterilization: during the treatment period and in the study treatment, the final use effective contraceptive methods for at least 6 months after a single administration.
6. Voluntarily join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up.

Exclusion Criteria:

1. Stage IV breast cancer.
2. Inflammatory breast cancer.
3. Previously received anti-tumor treatment or radiation therapy for any malignant tumor, excluding those that have been cured Malignant tumors such as cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma.
4. Simultaneously undergoing anti-tumor treatment in other clinical trials, including but not limited to chemotherapy and endocrine therapy. Treatment, biological therapy, bone improvement drug therapy, or immune checkpoint inhibitor therapy, etc.
5. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before the first administration of the study drug, or the patient has not fully recovered from such surgical procedures.
6. Serious heart disease or discomfort.
7. Uncontrolled active infections that require treatment; History of immunodeficiency, including HIV testing positive Sexual, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
8. Patients with chronic active hepatitis B or active hepatitis C
9. Have received immunotherapy and experienced adverse immune events such as immune related pneumonia and myocarditis, which have been determined by researchers to potentially affect the safety of the experimental medication.
10. Individuals with a known history of allergies to the components of this medication regimen.

Where this trial is running

Harbin and 4 other locations

• Harbin Medical University Cancer Hospital — Harbin, China (Recruiting)
• The First Affiliated Hospital of Anhui Medical University — Hefei, China (Recruiting)
• Zhongshan Hospital, Fudan University — Shanghai, China (Recruiting)
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an, China (Recruiting)
• The Second Affiliated Hospital of Xi'an Jiaotong University — Zhengzhou, China (Recruiting)

Study contacts

• Study coordinator: Zhijun Dai

Conditions HR Positive/HER2 Low Breast Cancer; Breast cancer; Toripalimab; Trastuzumab Rezetecan; Neoadjuvant therapy