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

Tianjin Medical University

Status and phase

Not yet enrolling

Phase 2

Conditions

Triple Negative Breast Cancer (TNBC)

PD-L1 Positive

Treatments

Drug: Sacituzumab Tirumotecan plus Tagitanlimab

Study type

Interventional

Funder types

Other

Identifiers

NCT07153965

SKB264-IIT-017

Details and patient eligibility

About

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.

Enrollment

47 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.