PD-L1 Positive, Triple Negative Breast Cancer (TNBC)
Conditions
Brief summary
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.
Interventions
DRUGSacituzumab Tirumotecan plus Tagitanlimab
Sacituzumab Tirumotecan 5mg/kg intravenously (IV) infusion every 2 weeks on Day 1, Tagitanlimab 900mg IV every 2 weeks on Day 1, until disease progression, unacceptable toxic effects, withdrawal from the trial, or death, whichever occurred first.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | up to approximately 60 months | ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Assessed by Investigator per RECIST Version 1.1 | up to approximately 60 months | PFS is defined as time from date of randomization until the date of first objective progressive disease (PD) by investigator assessment according to RECIST v1.1 or death from any cause, whichever comes first. |
| Overall Survival (OS) | up to approximately 60 months | OS is defined as the time from randomization until the date of death from any cause. |
| Disease control response (DCR) as Assessed by Investigator per RECIST Version 1.1 | up to approximately 60 months | DCR is defined as the proportion of participants who achieve a complete response (CR), partial response (PR) or or stable disease (SD) . |
| Safety and Tolerability | up to approximately 60 months | Incidence and severity of AEs and SAEs (per CTCAE 5.0) |
| Health-related quality of life (HRQoL) evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | up to approximately 60 months | Mean change from baseline in the EORTC QLQ-C30 |
| Health-related quality of life (HRQoL) evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module 23 (EORTC QLQ-BR23) | up to approximately 60 months | Mean change from baseline in the EORTC QLQ-BR23 |
| Duration of response (DoR) | up to approximately 60 months | DoR is defined as the time from the first objective response (CR/PR) to the first documented disease progression (PD) according to RECIST v1.1 or death from any cause, whichever comes first. |
Other
| Measure | Time frame | Description |
|---|---|---|
| TROP2, PD-L1, tumor-infiltrating lymphocytes (TILs), lymphocyte subpopulation | up to approximately 60 months | Explore potential biomarkers that predict the treatment response and prognosis of TNBC, including but not limited to the expression levels of TROP2, PD-L1, tumor-infiltrating lymphocytes (TILs), lymphocyte subpopulation. |
Countries
China
Contacts
Primary ContactYehui Shi
Outcome results
None listed