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
The purpose of this study is to assess the efficacy and safety of sitravatinib plus tislelizumab or combination with nab-paclitaxel in locally recurrent or metastatic triple-negative breast cancer (TNBC) patients.
This is a prospective, single-center, three cohorts, phase II clinical trial in locally recurrent or metastatic triple-negative breast cancer(TNBC) patients. Subjects will be divided into three cohorts by different treatment combination. Cohort A & Cohort B aim to explore the two dosages of sitravatinib in combination with tislelizumab in TNBC with prior ≤ 3 treatment line. Cohort A patients will receive 70mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV); Cohort B patients will receive 100mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV). Cohort C aims to explore the sitravatinib (QD PO) plus 200mg tislelizumab (Q3W IV) and 100 mg/m2 nab-paclitaxel (D1, D8 Q3W IV) in TNBC previously untreated for metastatic setting or recurred/metastasized after surgery. Subjects in the three cohorts will be treated until disease progression, intolerable toxicity, informed consent withdrawn, or investigators-determined medication termination. Drug efficacy and safety data will be collected.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | Subjects will receive 70mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
|
| Cohort B | Experimental | Subjects will receive 100mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
|
| Cohort C | Experimental | Subjects will receive sitravatinib in combination with 200mg tislelizumab and 100 mg/m2 nab-paclitaxel until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitravatinib | Drug | Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) by Investigator in Cohort A, Cohort B and Cohort C | The number of people with tumor responses according to RECIST (V1.1): the proportion of participants who achieves a best overall response of complete response (CR) or partial response (PR). | Up to 12 months |
| Number of participants experiencing ≥ Grade 3 TRAEs in Cohort B | TRAE are adverse events that occur during or after the first administration of the study drug until 30 days after the study drug is discontinued or the new anticancer treatment is initiated. | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Response (DOR) by Investigator in Cohort A, Cohort B and Cohort C | The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first. | Up to 12 months |
| Disease Control Rate (DCR) by Investigator in Cohort A, Cohort B and Cohort C |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Zhimin Shao, MD, PhD | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer | Shanghai | Shanghai Municipality | 200032 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Lei Fan, Xiyu Liu, Xi Jin, Yunsong Yang, Li Chen, Xin Hu, Zhonghua Wang, Yizhou Jiang, and Zhimin Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer.Journal of Clinical Oncology 2022 40:16_suppl, 1070-1070 | ||
| Result | L. Liu, X. Jin, Y. Xu, S. Wu, Y. Yang, L. Chen, W. Zhang, L. Ma, X. Hu, Z. Wang, Y. Jiang, Z. Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients (pts) with locally recurrent or metastatic triple negative breast cancer (TNBC): a multi-cohort, phase II trial. Annals of Oncology (2022) 16 (suppl_1): 100102-100102. 10.1016/iotech/iotech100102 | ||
| 41420248 | Derived | Liu XY, Sui XY, Xu Y, Yang F, Wu SY, Zhu XZ, Zuo K, Cao SW, Jin X, Chen L, Ma LX, Zhang WJ, Ye FG, Qu FL, Ma D, Xiao Y, Di GH, Liu GY, Yu KD, Wu J, Hu X, Jiang YZ, Wang ZH, Shao ZM, Fan L. Sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer: a multi-cohort, single-arm, phase II clinical trial (SPARK Trial). Mol Cancer. 2025 Dec 19;25(1):15. doi: 10.1186/s12943-025-02505-5. |
Not provided
Not provided
Not provided
Cohort A Subjects will receive 70mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Cohort B Subjects will receive 100mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Cohort C Subjects will receive sitravatinib in combination with 200mg tislelizumab and 100 mg/m2 nab-paclitaxel until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Not provided
Not provided
None (Open Label)
Not provided
|
| Tislelizumab | Drug | Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody |
|
|
| Nab-paclitaxel | Drug | Nab-paclitaxel D1, D8 Q3W IV Nab-paclitaxel is a chemotherapy drug which combines the chemotherapy drug paclitaxel with albumin |
|
|
The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD). |
| Up to 12 months |
| Progression-free Survival (PFS) by Investigator in Cohort A, Cohort B and Cohort C | Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first. | Up to 12 months |
| One-year overall survival (OS) rate in Cohort A, Cohort B and Cohort C | OS defined as the time from the date of randomization to the date of death due to any reason. One-year survival rate (percentage of subjects alive at 1 year) was estimated from OS data. | Up to 12 months |
| Number of participants experiencing Adverse Events (AEs), Treatment-Related Adverse Events (TRAEs) or Serious Adverse Events (SAEs) in Cohort A, Cohort B and Cohort C | Adverse Events (AEs) according to CTCAE v5.0 | Up to 12 months |
| Patient report outcomes (PROs) based on the EORTC QLQ-C30 (V.3) Quality of Life Questionnaire in Cohort B and Cohort C | Evaluating the Quality of Life of participants as assessed by EORTC QLQ-C30 Questionnaire | Through study completion, an average of 1 year |
| Potential biomarkers associated with efficacy, drug resistance, and/or disease progression (PD) in tumor tissues in Cohort A, Cohort B and Cohort C | Potential biomarkers in tumor tissues associated with efficacy | Through study completion, an average of 1 year |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D064726 | Triple Negative Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000611865 | sitravatinib |
| C000707970 | tislelizumab |
| C520255 | 130-nm albumin-bound paclitaxel |
| D013660 | Taxes |
| ID | Term |
|---|---|
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
Not provided
Not provided