JSKN003 versus physician's choice chemotherapy for HER2-low advanced breast cancer

A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

This trial will test whether the experimental drug JSKN003 works better than standard single‑agent chemotherapies for adults with HER2‑low, unresectable or metastatic breast cancer who have had one or two prior chemotherapy regimens.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 87 sites (Guangzhou, Guangdong and 86 other locations)
• Trial ID: NCT06079983 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label, multicenter phase III study enrolling 408 participants and using stratified block randomization to assign patients 1:1 to JSKN003 monotherapy or investigator's choice single‑agent chemotherapy. Eligible participants have HER2‑low disease (IHC 1+ or 2+/ISH‑) and have progressed after one or two prior lines of chemotherapy for recurrent or metastatic disease. The control options include capecitabine, gemcitabine, vinorelbine, docetaxel, albumin‑bound paclitaxel, or eribulin as single agents. The trial measures efficacy and safety outcomes to compare the experimental agent against commonly used chemotherapy options.

Who should consider this trial

Good fit: Adults (≥18) with unresectable locally recurrent or metastatic HER2‑low breast cancer (IHC 1+ or 2+/ISH‑), who have received one or two prior chemotherapy regimens for metastatic disease, have at least one measurable extracranial lesion, ECOG 0–1, expected survival ≥3 months, and can provide archived tumor tissue and informed consent.

Not a fit: Patients with HER2‑positive disease (IHC 3+ or ISH+), those who have received more than two prior lines of chemotherapy, have poor performance status (ECOG >1), very limited expected survival, or cannot provide required tissue are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If effective, JSKN003 could provide a more effective single‑agent treatment option that delays disease progression or improves clinical outcomes for patients with HER2‑low advanced breast cancer.

How similar studies have performed: Other programs targeting HER2‑low disease, most notably trastuzumab deruxtecan in DESTINY‑Breast04, have shown meaningful clinical benefit in this population, indicating the general approach has precedent even though JSKN003 itself is a different agent.

Eligibility criteria

Inclusion Criteria:

* 1\. The subject is able to understand the informed consent form, voluntarily participate and sign the informed consent form.

  2\. The subject ≥ 18 years old on the day of signing the informed consent form, male or female.

  3\. Unresectable locally recurrent or metastatic breast cancer, previous histopathological reports of HER2 IHC 1+ or 2+ and ISH-, previous histopathological reports have not been diagnosed as HER2 IHC 3+ or 2+ and ISH+.

  4\. Have received at least 1 to 2 lines of chemotherapy regimens for breast cancer in the relapse/metastatic stage.

  5\. Willing to provide sufficient archived tumor pathology specimens for central laboratory detection of HER2 status.

  6\. Documented radiographic disease progression (during or after the most recent treatment).

  7\. At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.

  8\. Expected survival ≥ 3 months. 9. ECOG score of 0 or 1 within 14 days prior to administration. 10. Female subjects of childbearing potential or male subjects of fertile partner consent to use highly effective contraception from the signing of informed consent.

  11\. Laboratory tests within 14 days before administration and cardiac function tests within 28 days meet the criteria.

  12\. Have sufficient elution of previous treatment before administration.

Exclusion Criteria:

* 1\. Untreated, or unstable brain parenchymal metastases, spinal cord metastases or compression, cancerous meningitis.

  2\. Patients with only skin lesions as target lesions. 3. Those with a history of other primary malignant tumors within 5 years before administration.

  4\. Selection of the control drug by the investigator who is not suitable for the protocol prescribed.

  5\. Previous use of antibody conjugates containing topoisomerase I inhibitors. 6. There is a third gap fluid that cannot be controlled by drainage, etc. 7. Previous or current interstitial pneumonia/lung disease requiring systemic hormone therapy.

  8\. Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that affect oral administration and absorption of the drug.

  9\. Previous or current autoimmune disease. 10. Have uncontrolled comorbidities. 11. The toxicity of previous antitumor therapy has not been restored to grade ≤1 (NCI-CTCAE v5.0).

  12\. History of previous immunodeficiency. 13. History of life-threatening allergic reactions or known ≥ grade 3 allergy to any component or excipient in the investigational pharmaceutical formulation.

  14\. Other conditions that the investigators believe will affect the safety or adherence to drug treatment in this study, including but not limited to psychiatric disorders, alcohol or drug abuse.

Where this trial is running

Guangzhou, Guangdong and 86 other locations

• Erwei Song — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Jiong Wu — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Anyang Cancer Hospital — Anyang, China (Not_yet_recruiting)
• Affiliated Hospital of Hebei University — Baoding, China (Not_yet_recruiting)
• Beijing Luhe Hospital — Beijing, China (Not_yet_recruiting)
• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, China (Recruiting)
• Peking University Cancer Hospital — Beijing, China (Recruiting)
• The First Affiliated Hospital of China Medical University — Beijing, China (Recruiting)
• The First Medical Center of the General Hospital of the People's Liberation Army Chinese People's Liberation Army — Beijing, China (Not_yet_recruiting)
• Bethune First Hospital of Jilin University — Changchun, China (Not_yet_recruiting)
• Jilin Provincial Cancer Hospital — Changchun, China (Not_yet_recruiting)
• The First People's Hospital of Changde — Changde, China (Recruiting)
• Central South University Xiangya Hospital — Changsha, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, China (Recruiting)
• Affiliated Hospital of Chengde Medical University — Chengde, China (Recruiting)
• Sichuan Cancer Hospital — Chengdu, China (Recruiting)
• Sichuan Provincial People's Hospital — Chengdu, China (Recruiting)
• West China Hospital, Sichuan University — Chengdu, China (Not_yet_recruiting)
• Cancer Hospital of Chongqing University — Chongqing, China (Not_yet_recruiting)
• The First Affiliated Hospital of Chongqing Medical University — Chongqing, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Dalian Medical University — Dalian, China (Not_yet_recruiting)
• Fujian Cancer Hospital — Fuzhou, China (Not_yet_recruiting)
• Fujian Provincial Hospital — Fuzhou, China (Recruiting)
• Union Hospital Affiliated to Fujian Medical University — Fuzhou, China (Recruiting)
• The First Affiliated Hospital of Gannan Medical University — Ganzhou, China (Recruiting)
• Guangdong Provincial People's Hospital — Guangzhou, China (Not_yet_recruiting)
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, China (Not_yet_recruiting)
• The Affiliated Hospital of Guangdong Medical University — Guangzhou, China (Recruiting)
• Sun Yat-sen University Cancer Center — Guanzhou, China (Not_yet_recruiting)
• Guizhou Provincial People's Hospital — Guiyang, China (Recruiting)
• The Affiliated Hospital of Guizhou Medical University — Guiyang, China (Recruiting)
• Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine — Hangzhou, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhejiang University School of Medicine — Hanzhou, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hanzhou, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hanzhou, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Ha’erbin, China (Not_yet_recruiting)
• Anhui Provincial Hospital — Hefei, China (Not_yet_recruiting)
• The First Affiliated Hospital of Anhui Medical University — Hefei, China (Not_yet_recruiting)
• The Second Affiliated Hospital of Anhui Medical University — Hefei, China (Not_yet_recruiting)
• The First Affiliated Hospital of University of South China — Hengyang, China (Recruiting)
• Affiliated Hospital of Inner Mongolia Medical University — Hohhot, China (Recruiting)
• Jiangmen Central Hospital — Jiangmen, China (Recruiting)
• Shandong Cancer Hospital — Jinan, China (Recruiting)
• Affiliated Hospital of Jining Medical University — Jining, China (Recruiting)
• Yunnan Cancer Hospital — Kunming, China (Not_yet_recruiting)
• Gansu Provincial Cancer Hospital — Lanzhou, China (Not_yet_recruiting)
• The First Hospital of Lanzhou University — Lanzhou, China (Recruiting)
• Linyi Cancer Hospital — Linyi, China (Not_yet_recruiting)
• Linyi People's Hospital — Linyi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Henan University of Science and Technology — Luoyang, China (Recruiting)

Study contacts

• Principal investigator: Erwei Song — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Erwei Song

Conditions Breast Cancer