Trastuzumab Rezetecan versus Trastuzumab Deruxtecan for unresectable HER2‑low, HR‑positive breast cancer

A Randomized, Open-Label, Multicenter Phase II Clinical Study of Different Doses of Trastuzumab Rezetecan for Injection or Trastuzumab Deruxtecan for Injection in the Treatment of Unresectable Locally Recurrent/Metastatic Breast Cancer With HR-Positive and HER2-Low Expression

This Phase 2 trial tests different doses of Trastuzumab Rezetecan compared with Trastuzumab Deruxtecan in women with HR-positive, HER2-low unresectable locally recurrent or metastatic breast cancer to see which dose is safer and more effective.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Trastuzumab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07497386 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial enrolls women aged 18–75 with HR-positive, HER2-low unresectable locally recurrent or metastatic breast cancer who progressed after endocrine therapy and have not received chemotherapy for metastatic disease. Participants receive injections of Trastuzumab Rezetecan at different dose levels or Trastuzumab Deruxtecan, with monitoring for tumor response and safety using RECIST v1.1 and standard clinical assessments. The protocol also includes exploratory pharmacokinetic and immunogenicity sampling to characterize drug levels and anti-drug antibodies. The trial is sponsored by Jiangsu HengRui Medicine and conducted at the Cancer Hospital, Chinese Academy of Medical Sciences in Beijing.

Who should consider this trial

Good fit: Women aged 18–75 with HR-positive, HER2-low unresectable locally recurrent or metastatic breast cancer who progressed after at least one line of endocrine therapy, have not received chemotherapy for metastatic disease, have ECOG 0–1, and at least one extracranial measurable lesion.

Not a fit: Patients whose tumors are not HER2-low, who have already received chemotherapy for metastatic disease, who have poor organ function or uncontrolled brain-only metastases, or who cannot comply with contraception or breastfeeding restrictions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the drugs could offer a new targeted treatment option and clearer dosing guidance for patients with HR-positive, HER2-low unresectable breast cancer.

How similar studies have performed: Other antibody–drug conjugates such as Trastuzumab Deruxtecan have shown clear benefit in HER2-low breast cancer in prior trials, while Trastuzumab Rezetecan is a newer agent with limited clinical data to date.

Eligibility criteria

Inclusion Criteria:

1. Female aged 18 to 75 years (inclusive).
2. Unresectable locally recurrent or metastatic breast cancer.
3. Prior therapy must meet the following: No prior chemotherapy for recurrent/metastatic disease. Must have received at least one prior line of endocrine therapy for recurrent/metastatic disease with disease progression, and the investigator judges that further benefit from endocrine therapy is not possible.
4. Documented radiological disease progression (during or after the most recent therapy).
5. ECOG performance status of 0 or 1.
6. Life expectancy ≥ 12 weeks.
7. At least one extracranial measurable lesion as a target lesion according to RECIST v1.1 criteria.
8. Adequate function of major organs.
9. Pregnancy and contraception: Women of childbearing potential (WOCBP) must agree to use highly effective contraception from study screening until 7 months after the last dose of study drug and agree not to breastfeed; serum pregnancy test result must be negative within 7 days before the first dose.
10. The patient voluntarily participates in this study, signs the informed consent form, has good compliance, and is willing to cooperate with visits and study-related procedures.

Exclusion Criteria:

1. Presence of leptomeningeal metastasis/carcinomatous meningitis, spinal cord compression, or active central nervous system metastases.
2. Patients with only skin or brain lesions as target lesions.
3. History of other malignancies within the past 5 years, except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix.
4. Presence of carcinomatous lymphangitis, or third-space fluid accumulation that cannot be controlled by methods such as drainage.
5. Prior surgery, chemotherapy, immunotherapy, or macromolecular targeted therapy within 4 weeks before the first dose; prior endocrine therapy, chemotherapy with 5-FU analogs, or radiotherapy within 2 weeks before the first dose; small molecule targeted agents require a washout period of 2 weeks or 5 half-lives; other investigational drugs require a washout period of 4 weeks or 5 half-lives before the first dose.
6. Use of immunosuppressants or systemic corticosteroids for immunosuppressive purposes within 2 weeks before the first dose for therapeutic intent.
7. History of immunodeficiency, including a positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
8. Clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure, etc.; clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; myocardial infarction or cerebrovascular accident within 6 months before the first dose.
9. Participants with known or suspected interstitial lung disease; other moderate-to-severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity and severely affect respiratory function within 3 months before the first dose; and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
10. Known hereditary or acquired bleeding tendency.
11. Active hepatitis B, hepatitis C, or cirrhosis; or severe infection requiring control with antibiotics, antivirals, or antifungals.
12. Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 1 (according to NCI-CTCAE v5.0).
13. Any other severe physical or mental illness or laboratory abnormality that may increase the risk associated with study participation, interfere with study results, or any other condition for which the investigator considers the patient unsuitable for participation in this study.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Xia Zhang

Conditions Unresectable Locally Recurrent Breast Cancer; Unresectable Locally Metastatic Breast Cancer