Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sacituzumab Tirumotecan (Sac-TMT) plus Bevacizumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sacituzumab Tirumotecan (Sac-TMT) | Drug | Eligible patients will receive a dosage of sac-TMT 4mg/kg Q2W |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| CNS CBR | 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. | from enrollment to progression or death (for any reason), assessed up to 24 months |
| Progression-free survival |
Not provided
Inclusion Criteria:
(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:
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:
History of allergy or hypersensitivity to any of the study drugs or study drug components;
History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation;
A clear history of neurological or mental disorders, including epilepsy or dementia;
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);
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;
Any condition which in the investigators' opinion makes the subjects unsuitable for the study participation.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Biyun Wang | Contact | 18017312387 | pro_wangbiyun@163.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200000 | China |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| bevacizumab | Drug | safety run-in phase: bevacizumab 10mg/kg D1 Q2W Dose expansion phase: bevacizumab RP2D D1 Q2W |
|
PFS will be defined as the time from the first dose of treatment to death or disease progression |
| Up to 2 years |
| Overall survival | OS will be defined as the time from the first dose of treatment to death for any cause | Up to 2 years |
| First progression site | The first lesion to progress | Up to 2 years |
| Safety as assessed by percentage of patients with any Adverse Event | Adverse event according to NCI-CTC AE 5.0 | Up to 2 years |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |