Sacituzumab Tirumotecan Plus Tagitanlimab in Previously Treated Locally Advanced or Metastatic Triple Negative Breast Cancer

An Open-label, Single-arm, Multicenter Phase II Study of Sacituzumab Tirumotecan (Sac-TMT) Plus Tagitanlimab in Previously Treated PD-L1-positive Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)

This is an open-label, single-arm, multicenter phase II study to evaluate the safety and efficacy of sac-TMT plus Tagitanlimab in patients with PD-L1-positive locally advanced or metastatic TNBC.

Key inclusion criteria include but are not limited to:

• Age ≥ 18 years at the time of signing informed consent.

• Histologically and/or cytologically confirmed triple-negative breast cancer (TNBC) based on the most recent biopsy or other pathological specimens, including:

  1. Definition of human epidermal growth factor receptor 2 (HER2) negative: immunohistochemistry (IHC) of 0 or 1+; if HER2 is 2+ by IHC, negative HER2 expression must be confirmed by fluorescencein situ hybridization (FISH); Estrogen and progesterone receptor negative means that less than 1% of the cells express hormone receptors as indicated by IHC.
  2. Tumor stage: locally advanced, recurrent, or metastatic TNBC; locally advanced cases must be confirmed by the investigator as unsuitable for curative surgical resection.

• Patients with unresectable locally advanced or metastatic triple-negative breast cancer:

  1. Those who have received chemotherapy combined with a PD-(L)1 inhibitor as first-line treatment for locally advanced or metastatic disease and experienced progression ≥ 3 months later.
  2. Those who received chemotherapy combined with a PD-(L)1 inhibitor in the neoadjuvant and/or adjuvant setting and experienced recurrence or disease progression to unresectable locally advanced or metastatic disease ≥ 3 months later but within 12 months.
  3. Those who received chemotherapy combined with a PD-(L)1 inhibitor in the neoadjuvant and/or adjuvant setting and experienced recurrence or disease progression to unresectable locally advanced or metastatic disease after ≥ 12 months, and have subsequently progressed on first-line treatment for locally advanced or metastatic disease.

• Newly diagnosed brain metastases at screening must be stable for ≥ 4weeks after local treatment (e.g., radiotherapy) with imaging confirmation.

• The most recent tumor tissue sample from the primary and/or metastatic lesion must show a PD-L1 combined positive score (CPS) ≥ 1.

• Patients must have at least one measurable lesion per RECIST v1.1 criteria; those with only skin or bone lesions cannot be included.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to1.

• Patients must have adequate organ and bone marrow function (no blood transfusion, recombinant human thrombopoietin, or colony stimulating factor therapy has been received within 2 weeks prior to the treatment)

• Patients of childbearing potential (male or female) must use effective medical contraception from consent until 6 months after the end of the dosing period.

Key exclusion criteria include but are not limited to:

• Previously received any of the following treatments (including in the adjuvant or neoadjuvant setting):

  1. Targeted TROP2 therapy.
  2. Any drug treatment targeting topoisomerase I, including antibody drug conjugates (ADC) therapy.

• Known to have meningeal metastasis, brainstem metastasis, spinalcord metastasis, and/or compression, active central nervous system(CNS) metastasis. Patients with previously treated brain metastases canparticipate if clinically stable for at least 4 weeks before dosing and do not require corticosteroids or anticonvulsants for at least 14 days. Patients with untreated asymptomatic brain metastases must require investigator approval.

• Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing.

• Within 3 years before administration having other malignancies (except forthose cured by local treatment, such as basal cell carcinoma of the skin,squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).

• Has uncontrolled, significant cardiovascular disease or risk factors, uncontrollable systemic diseases.

• Presence of steroid-requiring (non-infectious) interstitial lung disease (ILD)or a history of non-infectious pneumonia, currently having ILD or non-infectious pneumonia, or suspected ILD or non-infectious pneumonia that cannot be ruled out by imaging at screening.

• Unresolved toxicities from previous anti-tumor therapy to ≤ Grade 1 (based on NCI CTCAE v5.0) or the level specified in the inclusion and exclusion criteria.

• Patients with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.

• Having an active autoimmune disease requiring systemic treatment inthe past two years.

• Known active tuberculosis, hepatitis B or hepatitis C.

• Human Immunodeficiency Virus (HIV) test positive or history of Acquired Immunodeficiency Syndrome (AIDS); known active syphilis infection.

• Known allergy to the study drug or any of its components, known history of severe hypersensitivity to other biological products

• Pregnant or breastfeeding women.