Sac-TMT Combined With Bevacizumab in TNBC With Brain Metastases

NCT07623577 | Recruiting Phase 2

• 1 other identifier: BCBM-007
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, multi-center phase II study to evaluate the safety and efficacy Sacituzumab Tirumotecan (Sac-TMT) plus bevacizumab in triple-negative breast cancer patients with brain metastases. Twenty-four participants are planned to be enrolled. The eligible patients should have histologically or cytologically confirmed TNBC with BM.

Conditions

TNBC; Brain Metastasis

Keywords

trop2; Bevacizumab; Sacituzumab Tirumotecan; TNBC; brain metastasis

Outcome Measures

Primary Outcomes (1)

• CNS ORR

  The proportion of patients who have a CR or PR in the CNS, as determined by the Investigator according to RANO-BM criteria

  from enrollment to progression or death (for any reason), assessed up to 24 months

Secondary Outcomes (5)

• CNS CBR

  from enrollment to progression or death (for any reason), assessed up to 24 months

• Progression-free survival

  Up to 2 years

• Overall survival

  Up to 2 years

• First progression site

  Up to 2 years

• Safety as assessed by percentage of patients with any Adverse Event

  Up to 2 years

Study Arms (1)

Sacituzumab Tirumotecan (Sac-TMT) plus Bevacizumab

EXPERIMENTAL

Drug: Sacituzumab Tirumotecan (Sac-TMT); Drug: bevacizumab

Interventions

Sacituzumab Tirumotecan (Sac-TMT) DRUG

Eligible patients will receive a dosage of sac-TMT 4mg/kg Q2W

Sacituzumab Tirumotecan (Sac-TMT) plus Bevacizumab

bevacizumab DRUG

safety run-in phase: bevacizumab 10mg/kg D1 Q2W Dose expansion phase: bevacizumab RP2D D1 Q2W

Sacituzumab Tirumotecan (Sac-TMT) plus Bevacizumab

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 old, regardless of gender;
• ECOG Performance Status of 0-2;
• Histologically or cytologically confirmed HR-negative and HER2-negative breast cancer; there is evidence of metastasis; not suitable with curative surgery or radiation therapy; HR negative is defined as: ER-negative and PR-negative, the proportion of positively stained tumor cells in all tumor cells is \< 10%; HER2- negative is defined as: histologically confirmed to be HER2 IHC (0) or HER2 IHC(1+) or HER2 IHC (2+) and FISH(-);
• MRI confirmed brain metastases, at least one intracranial parenchymal metastatic lesion with a longest diameter ≥ 1.0 cm without prior radiotherapy; For lesions with prior radiotherapy, progressive disease post radiotherapy must be confirmed by MRI
• Any conditions deemed by the investigator to make the patient unnecessary for local therapy;
• Life-expectancy ≥ 3 months;
• Intraventricular catheter shunt to reduce intracranial pressure or treatment with mannitol, hormones, and anticonvulsants was permitted prior to the first dose, but the dose of medication was stable for at least one week without increment and neurological symptoms were stable for ≥1 week;
• Adequate function of major organs meets the following requirements:
• (1)Blood routine: ANC≥1.5×109/L; PLT≥75×109/L; Hb ≥90 g/L(Allows blood transfusion or the use of medication to ensure that the content of hemoglobin) ; (2)Coagulation: INR≤1.5; APTT≤1.5×ULN ; (3)Blood biochemistry：TBIL≤1.5 × ULN; ALT and AST≤3 × ULN (liver metastasis≤5.0 × ULN); Urea nitrogen ≤1.5 × ULN; Cr≤1.5 × ULN or creatinine clearance ≥50 mL / min (Cockcroft-Gault formula) ; (4)Cardiac ultrasound: LVEF≥50%; (5)12-lead ECG: females QTcF interval \< 470 ms and males \< 450 ms; 9. Willing to join the study, sign informed consent, have good compliance and can cooperate with follow-up.

You may not qualify if:

• Pial metastases confirmed by MRI or lumbar puncture;
• Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites);
• Whole brain radiotherapy, chemotherapy, biological targeted therapy, immunotherapy, surgery or endocrine therapy within 2 weeks prior to enrolment;
• Prior use of bevacizumab or other anti-angiogenic agents is prohibited, except for the following scenarios:a)No disease progression occurred during bevacizumab treatment, no confirmed drug resistance was identified, and the investigator deems continued use beneficial for the participant;b)Short-course bevacizumab was administered solely for the management of cerebral edema
• Has received prior therapy with topoisomerase I inhibitors and ADC drugs regardless of targeting any target;
• Participation in any other clinical trials 2 weeks before enrollment;
• Strong inhibitors or inducers of CYP3A4 are not permitted during the study, which includes the 4-week period prior to the first administration.
• Concurrent use of any other Anti-cancer drugs;
• Bleeding tendency such as acute gastrointestinal bleeding, persistent bleeding disease or coagulation dysfunction;
• Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma;
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment, a current ILD or non-infectious pneumonia, or a suspected ILD or non-infectious pneumonia that could not be ruled out by imaging at the time of screening; Clinically severe lung impairment due to co-occurring lung disease, including but not limited to any underlying lung disease (pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs , or prior total pulmonary resection;
• History of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease that interferes with delayed corneal healing;
• Severe infection within 4 weeks prior to initial dosing, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; Active infections requiring systemic anti-infective therapy were present within 2 weeks prior to initial administration;
• History of heart disease:
• Arrhythmias requiring medical treatment or of clinical significance;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Biyun Wang

CONTACT

18017312387; pro_wangbiyun@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a single-arm, multi-center phase II study to evaluate the safety and efficacy Sacituzumab Tirumotecan (Sac-TMT) plus bevacizumab in triple-negative breast cancer patients with brain metastases. Twenty-four participants are planned to be enrolled. The eligible patients should have histologically or cytologically confirmed TNBC with BM. This study includes a safety run-in period followed by an expansion cohort. The safety run-in period will employ the mTPI-2 (modified toxicity probability interval-2) design for an initial safety assessment. In Dose Expansion stage, 24 eligible patients will receive a dosage of sac-TMT 4mg/kg Q2W and the recommended dosage of bevacizumab in safety run-in period. Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint is CNS ORR and secondary endpoints include CNS CBR, systemic ORR, PFS, OS, safety and tolerability.

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: June 3, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 3, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)