Clinical trial NCT06849492: HIM Typing Guides the Treatment of Advanced First-Line Triple-Negative Breast Cancer
Official title: An Open, Multicenter Study on the Treatment of Recurrent and Metastatic Triple-negative Breast Cancer Guided by Cell Surface Protein Typing (HIM) in Triple-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Triple Negative Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: ORR
timeFrame: at the time point of every 12 weeks, up to one year
Secondary outcomes:
measure: CBR
timeFrame: up to 2 years
measure: DoR
timeFrame: up to 2 years
measure: PFS
timeFrame: up to 2 years
measure: OS
timeFrame: up to 3 years
measure: Safety
timeFrame: from time of informed consent provided to 3 months after the last dose of study therapy
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan Cancer Hospital
state: Shanghai
Study officials:
References: