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

NCT06849492 | Not Yet Recruiting Phase 2

• 1 other identifier: SHIFT-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• CBR

  up to 2 years

• DoR

  up to 2 years

• PFS

  up to 2 years

• OS

  up to 3 years

• Safety

  from time of informed consent provided to 3 months after the last dose of study therapy

Study Arms (3)

Cohort A (H subtyping)

EXPERIMENTAL

Drug: Camrelizumab; Drug: Nab-paclitaxel

Cohort B (I subtyping)

EXPERIMENTAL

Drug: SKB264

Cohort C (M subtyping)

EXPERIMENTAL

Drug: Camrelizumab; Drug: Nab-paclitaxel; Drug: Lenvatinib

Interventions

Camrelizumab DRUG

PD-1 inhibitor

Cohort A (H subtyping); Cohort C (M subtyping)

Nab-paclitaxel DRUG

chemotherapy

Cohort A (H subtyping); Cohort C (M subtyping)

SKB264 DRUG

Trop2-ADC

Cohort B (I subtyping)

Lenvatinib DRUG

Anti-angiogenic TKI

Cohort C (M subtyping)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• More than 18 years old;
• ECOG PS Score: 0\~1;
• Patients must have a life expectancy ≥ 3 months;
• 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%)；
• At least one measurable lesion according to RECIST 1.1 criteria；
• No prior systemic anti-tumor therapy during the recurrent or metastatic stage；
• 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)；
• Adequate organ function and marrow function;
• Willing to join in this study, able to provide written informed consent, good compliance and willing to cooperate with follow-up.

You may not qualify if:

• Has leptomeningeal metastasis or cystic metastatic lesions confirmed by MRI or lumbar puncture;
• Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g.；
• Received systemic anti-tumor therapy within 14 days prior to enrollment;
• 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；
• 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；
• 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)；
• 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;
• 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);
• 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;
• Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia, etc.);
• 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;
• 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;
• 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;
• History of or planned allogeneic bone marrow transplantation or solid organ transplantation;
• Peripheral neuropathy ≥ grade 2;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Interventions

camrelizumab; 130-nm albumin-bound paclitaxel; lenvatinib

Central Study Contacts

Mingchuan Zhao, Associate chief physician

CONTACT

+86 13661940232; aeoluszmc@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: February 16, 2025
• First Posted: February 27, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)