HIM Typing Guides the Treatment of Advanced First-Line Triple-Negative Breast Cancer

NCT ID: NCT06849492

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2028-12-31

Brief Summary

To explore the efficacy and safety of treatment for recurrent and metastatic advanced first-line triple-negative breast cancer guided by cell surface protein-based subtyping (HIM).

Conditions

Advanced Triple Negative Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A (H subtyping)

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

PD-1 inhibitor

Nab-paclitaxel

Intervention Type: DRUG

chemotherapy

Cohort B (I subtyping)

Group Type: EXPERIMENTAL

SKB264

Intervention Type: DRUG

Trop2-ADC

Cohort C (M subtyping)

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

PD-1 inhibitor

Nab-paclitaxel

Intervention Type: DRUG

chemotherapy

Lenvatinib

Intervention Type: DRUG

Anti-angiogenic TKI

Interventions

Camrelizumab

PD-1 inhibitor

Intervention Type: DRUG

Nab-paclitaxel

chemotherapy

Intervention Type: DRUG

SKB264

Trop2-ADC

Intervention Type: DRUG

Lenvatinib

Anti-angiogenic TKI

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. More than 18 years old;

2. ECOG PS Score: 0~1;

3. Patients must have a life expectancy ≥ 3 months;

4. Histopathologically confirmed recurrent metastatic triple-negative invasive breast cancer (HER2-negative: IHC 0/1+ or IHC 2+ with negative ISH; ER-negative: IHC <1%, PR-negative: IHC <1%)；

5. At least one measurable lesion according to RECIST 1.1 criteria；

6. No prior systemic anti-tumor therapy during the recurrent or metastatic stage；

7. Sufficient tissue samples for HIM subtyping analysis (at least 15 unstained slides from the most recent metastatic lesion biopsy are required; primary lesion samples from treatment-naive patients are acceptable, and re-biopsy samples from such patients are also acceptable)；

8. Adequate organ function and marrow function;

9. Willing to join in this study, able to provide written informed consent, good compliance and willing to cooperate with follow-up.

Exclusion Criteria

1. Has leptomeningeal metastasis or cystic metastatic lesions confirmed by MRI or lumbar puncture;

2. Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g.；

3. Received systemic anti-tumor therapy within 14 days prior to enrollment;

4. Imaging shows tumor invasion of major blood vessels, or the investigator judges that the tumor is highly likely to invade critical vessels during the study period, leading to life-threatening hemorrhage；

5. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, serum calcium > 12 mg/dL, or albumin-corrected serum calcium > ULN); or symptomatic hypercalcemia requiring ongoing bisphosphonate therapy；

6. Prior treatment with immune checkpoint inhibitors other than PD-1/PD-L1 monoclonal antibodies (including but not limited to CTLA-4 antibodies, etc.), or anti-angiogenic agents (including monoclonal antibodies and TKIs)；

7. History of other malignancies within the past 5 years, having received any systemic anti-tumor therapy or local treatment (including surgery and radiotherapy) for malignancies, excluding cured in situ carcinomas, cervical carcinoma, basal cell carcinoma, squamous cell carcinoma, thyroid carcinoma, and other malignancies;

8. Major surgery unrelated to breast cancer within 4 weeks prior to enrollment, or the patient has not fully recovered from such surgical procedures (tissue biopsy for diagnostic purposes and peripherally inserted central catheter placement are allowed);

9. Any known or suspected autoimmune disease, except for: hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy; or stable type I diabetes with controlled blood glucose;

10. Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia, etc.);

11. History of live or attenuated live vaccination within 28 days prior to the first study dose or planned live or attenuated live vaccination during the study period;

12. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); active hepatitis (hepatitis B, defined as HBV-DNA ≥ 30 copies/ml; hepatitis C, defined as HCV-RNA above the lower limit of detection of the assay method) or co-infection with hepatitis B and C; autoimmune hepatitis;

13. Severe infections within 4 weeks prior to the first dose, including but not limited to bacteremia or severe pneumonia requiring hospitalization; or active infections requiring systemic antibiotic treatment with CTCAE ≥ grade 2 within 2 weeks prior to the first dose; or unexplained fever > 38.5°C during screening or prior to the first dose (fever due to tumor-related causes, as judged by the investigator, is allowed); evidence of active tuberculosis infection within 1 year prior to dosing;

14. History of or planned allogeneic bone marrow transplantation or solid organ transplantation;

15. Peripheral neuropathy ≥ grade 2;

16. Severe cardiac disease or conditions；

17. Subjects who have received systemic immunostimulant therapy (including but not limited to interferon or interleukin-2, including immunostimulants in clinical research stages) within 4 weeks prior to the first dose;

18. Subjects who have received systemic immunosuppressive therapy (including but not limited to glucocorticoids, azathioprine, methotrexate, thalidomide, anti-tumor factor drugs) within 2 weeks prior to the first dose. This exclusion does not apply to intranasal and inhaled corticosteroids or physiological doses of systemic steroid hormones (i.e., no more than 10 mg/day prednisone or equivalent doses of other corticosteroids)；

19. Known allergy to the investigational drug or any of its excipients; or a history of severe allergic reactions to other monoclonal antibodies;

20. Female patients during the gestation or suckling period, of childbearing potential and pregnancy test-positive, or unwilling to use an effective method of contraception during the whole study;

21. A documented history of neurological or psychiatric disorders, including epilepsy or dementia, or a known history of substance abuse, alcoholism, or drug addiction.

22. Any other conditions not appropriate for study enrolment in the opinion of the investigator.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Hongxia Wang

Chief physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan Cancer Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Mingchuan Zhao, Associate chief physician

Role: CONTACT

aeoluszmc@gmail.com

+86 13661940232

Facility Contacts

Fudan Cancer Hospital

Role: primary

whx365@126.com

+8621-38196379

Other Identifiers

SHIFT-001

Identifier Type: -

Identifier Source: org_study_id