Sacituzumab Tirumotecan Plus Anlotinib for Metastatic Triple Negative Breast Cancer

NCT07139470 | Not Yet Recruiting Phase 1

• 1 other identifier: SKB264-IIT-001
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, multicenter phase I/II study to evaluate the safety and efficacy of sac-TMT plus anlotinib in previously treated mTNBC. The study is expected to enroll up to 59 eligible patients.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Objective response rate (ORR)

  The primary endpoint of Phase I. 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. Radiographic assessment of tumor response will be performed based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1

  up to approximately 60 months

• Safety and the recommended phase 2 dose (RP2D)

  The primary endpoint of Phase II. BOIN design was used to evaluate the safety and the recommended phase 2 dose (RP2D) of sac-TMT plus anlotinib

  Up to Day 21

Secondary Outcomes (7)

• Disease control response (DCR)

  up to approximately 60 months.

• Duration of response (DOR)

  up to approximately 60 months

• Progression-free survival (PFS)

  up to approximately 60 months

• Overall Survival (OS)

  Until death, up to approximately 60 months.

• 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) scale

  up to approximately 60 months

Other Outcomes (3)

• Clinical benefit according to TROP2 expression at baseline.

  up to approximately 60 months

• Clinical benefit according to homologous recombination deficiency (HRD) at baseline

  up to approximately 60 months

• Clinical benefit according to angiogenesis gene profiles at baseline

  up to approximately 60 months

Study Arms (1)

sac-TMT+anlotinib

EXPERIMENTAL

In the Phase I part, BOIN design was used. There were 3 prespecified doses (sac-TMT 4mg/kg Q2W +anlotinib 8mg Q3W, sac-TMT 4mg/kg Q2W +anlotinib10mg Q3W, sac-TMT 4mg/kg Q2W +anlotinib12 mg Q3W). In the Phase II part, the patients will receive sac-TMT patients Q2W +anlotinib RP2D Q3W. The treatment will continue until disease progression, unacceptable toxic effects, withdrawal from the trial, or death, whichever occurred first.

Drug: Sacituzumab Tirumotecan + anlotinib

Interventions

Sacituzumab Tirumotecan + anlotinib DRUG

Phase I part: 3 prespecified doses (sac-TMT 4mg/kg Q2W +anlotinib 8mg Q3W, sac-TMT 4mg/kg Q2W +anlotinib10mg Q3W, sac-TMT 4mg/kg Q2W +anlotinib12 mg Q3W). Phase II part: sac-TMT patients Q2W +anlotinib RP2D Q3W.

sac-TMT+anlotinib

Eligibility Criteria

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

You may qualify if:

• 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 pathological specimen, including:
• Definition of human epidermal growth factor receptor 2 (HER2) negative: immunohistochemistry (IHC) of 0 or 1+; if HER is 2+ by IHC, negative HER2 expression must be confirmed by fluorescence in situ hybridization (FISH);
• Estrogen and progesterone receptor negative means that less than 1% of the cells express hormone receptors as indicated by IHC.
• Patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received at least one line of standard of care regimens, including:
• Any treatment received by the patients regardless of triple-negative state can be included as one of the standard of care regimens;
• For neoadjuvant and/or adjuvant chemotherapy, if relapse or disease progression to unresectable locally advanced or metastatic disease occurs during treatment or within 12 months after discontinuation of treatment (at least 2 cycles have been completed), it will be considered as one of the standard of care regimens;
• For patients with documented germline BRCA1/BRCA2 mutations, if they have been treated with an approved PARP inhibitor, then the PARP inhibitor can be considered as one prior standard of care regimens required;
• Patients must have progressed on or were intolerable to the treatment during or after the last treatment prior to enrollment.
• Newly diagnosed brain metastases at screening must be stable for ≥4 weeks after local treatment (e.g., radiotherapy) with imaging confirmation.
• 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 to 1.
• With an expected survival of ≥ 12 weeks.
• 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), which is defined as follows:
• Hematology: neutrophil count (NEUT) ≥ 1.5 × 10\^9/L; platelets (PLT) ≥ 100 × 10\^9/L; hemoglobin ≥ 90g/L;

You may not qualify if:

• Previously received any of the following treatments (including in the adjuvant or neoadjuvant setting):
• TargetedTROP2therapy;
• Any drug treatment targeting topoisomeraseI, including antibody-drug conjugates (ADC) therapy;
• Anti-angiogenic drugtherapy.
• Patients with multiple factors affecting oral medication.
• Known to have meningeal metastasis, brainstem metastasis, spinal cord metastasis, and/or compression, active central nervous system (CNS) metastasis. Patients with previously treated brain metastases can participate 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.
• Within 3 years before administration having other malignancies (except for those cured by local treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).
• Presence of any of the following cardiovascular diseases or risk factors:
• Within 6 months before administration, myocardial infarction, unstable angina, acute or persistent myocardial ischemia, grade 3 or grade 4 heart failure, symptomatic or poorly controlled severe arrhythmias, cerebrovascular accident, transient ischemic attack, and other severe cardiovascular diseases;
• History of myocarditis, primary cardiomyopathy, specific cardiomyopathy, and other myocardial diseases;
• Within 3 months before administration, any deep vein thrombosis (if stabilized by low molecular weight heparin or similar drugs≥ 2 weeks, enrollment is allowed), peripheral arterial thromboembolism, pulmonary embolism, or other severe thromboembolic events;
• Presence of aortic aneurysm, aortic dissection aneurysm, or other major vascular diseases that may be life-threatening or require surgery within 6 months before administration.
• Uncontrollable systemic diseases as judged by the investigator:
• Poorly controlled diabetes (fasting blood glucose≥ 10 mmol/L on two consecutive occasions);
• Poorly controlled hypertension (systolic blood pressure\> 160 mmHg and/or diastolic blood pressure\> 100 mmHg);

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Cancer Hospital Airport Hospital

Tianjin, Tianjin Municipality, 300000, China

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Chunfang Hao

CONTACT

86-022-60670123 Ext. 3805; haochunfang@tjmuch.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2025
• First Posted: August 24, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): October 15, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Locations

CN (1)