Brain Metastasis, TNBC
Conditions
Keywords
trop2, Bevacizumab, Sacituzumab Tirumotecan, TNBC, brain metastasis
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.
Interventions
Eligible patients will receive a dosage of sac-TMT 4mg/kg Q2W
DRUGbevacizumab
safety run-in phase: bevacizumab 10mg/kg D1 Q2W Dose expansion phase: bevacizumab RP2D D1 Q2W
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old, regardless of gender; 2. ECOG Performance Status of 0-2; 3. 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(-); 4. 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 5. Any conditions deemed by the investigator to make the patient unnecessary for local therapy; 6. Life-expectancy ≥ 3 months; 7. 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; 8. 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.
Exclusion criteria
1. Pial metastases confirmed by MRI or lumbar puncture; 2. Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites); 3. Whole brain radiotherapy, chemotherapy, biological targeted therapy, immunotherapy, surgery or endocrine therapy within 2 weeks prior to enrolment; 4. 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 5. Has received prior therapy with topoisomerase I inhibitors and ADC drugs regardless of targeting any target; 6. Participation in any other clinical trials 2 weeks before enrollment; 7. Strong inhibitors or inducers of CYP3A4 are not permitted during the study, which includes the 4-week period prior to the first administration. 8. Concurrent use of any other Anti-cancer drugs; 9. Bleeding tendency such as acute gastrointestinal bleeding, persistent bleeding disease or coagulation dysfunction; 10. Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma; 11. 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; 12. History of severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease that interferes with delayed corneal healing; 13. 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; 14. History of heart disease: 1. Arrhythmias requiring medical treatment or of clinical significance; 2. Myocardial infarction; 3. Heart failure; 4. Any heart diseases that investigator believes not suitable for this study; 15. History of allergy or hypersensitivity to any of the study drugs or study drug components; 16. History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation; 17. A clear history of neurological or mental disorders, including epilepsy or dementia; 18. According to the investigators' judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs); 19. Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation; 20. Any condition which in the investigators' opinion makes the subjects unsuitable for the study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CNS ORR | from enrollment to progression or death (for any reason), assessed up to 24 months | The proportion of patients who have a CR or PR in the CNS, as determined by the Investigator according to RANO-BM criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CNS CBR | from enrollment to progression or death (for any reason), assessed up to 24 months | CNS clinical benefit rate (CBR) will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 24 weeks. |
| Progression-free survival | Up to 2 years | PFS will be defined as the time from the first dose of treatment to death or disease progression |
| Overall survival | Up to 2 years | OS will be defined as the time from the first dose of treatment to death for any cause |
| First progression site | Up to 2 years | The first lesion to progress |
| Safety as assessed by percentage of patients with any Adverse Event | Up to 2 years | Adverse event according to NCI-CTC AE 5.0 |
Countries
China
Contacts
CONTACTBiyun Wang
Outcome results
None listed