HIM Typing Guides the Treatment of Advanced First-Line Triple-Negative Breast Cancer (SHIFT-001)

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Camrelizumab; Drug: SKB264; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingchuan Zhao, Associate chief physician; Phone Number: +86 13661940232; Email: aeoluszmc@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan Cancer Hospital
      • Contact: Fudan Cancer Hospital; Phone Number: +8621-38196379; Email: whx365@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (H subtyping)	Drug: Nab-paclitaxel; chemotherapy; Drug: Camrelizumab; PD-1 inhibitor
Experimental: Cohort B (I subtyping)	Drug: SKB264; Trop2-ADC
Experimental: Cohort C (M subtyping)	Drug: Nab-paclitaxel; chemotherapy; Drug: Camrelizumab; PD-1 inhibitor; Drug: Lenvatinib; Anti-angiogenic TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR is the percentage of evaluable patients with a confirmed investigator-assessed target lesion response of CR (complete response) or PR (partial response) per RECIST 1.1	at the time point of every 12 weeks, up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DoR	DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.	up to 2 years
CBR	CBR is the percentage of evaluable patients with a confirmed investigator-assessed target lesion response of CR (complete response) or PR (partial response) or at least 6 months of SD (stable disease) per RECIST 1.1	up to 2 years
PFS	PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).	up to 2 years
OS	OS is the time from the date of first dose until the date of death by any cause.	up to 3 years
Safety	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experienced an adverse event and discontinued study drug due to an AE.	from time of informed consent provided to 3 months after the last dose of study therapy

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 16, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Lenvatinib; Paclitaxel
• Other Study ID Numbers: SHIFT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No