A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib Plus Tislelizumab or Combination With Nab-paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC)

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 Subjects in the three cohorts will be treated until disease progression, intolerable toxicity, informed consent withdrawn, or investigators-determined medication termination.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.

Inclusion criteria

• Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
• Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
• Histologically confirmed diagnosis of TNBC characterized by estrogen-receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2 receptor negative (HER2-);
• ≤ 3 prior lines of systemic therapy
• For patients refractory/resistant to anti-PD-1/PD-L1 antibodies, there should be no anti-PD-1/PD-L1 treatment-related toxicity from prior therapies
• Previously untreated for metastatic setting or recurred/metastasized after surgery for locally recurrent or metastatic breast cancer (cohort C), and the time from previous neo-/adjuvant therapy to recurrence met the following requirements: ≥ 6 months interval between the end of neo-/adjuvant paclitaxel-based treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant anti-angiogenic treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant immunotherapy and recurrence/metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
• Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)

Exclusion criteria

• Active leptomeningeal disease or uncontrolled brain metastasis
• Active autoimmune diseases or history of autoimmune diseases that may relapse
• Any active malignancy ≤ 2 years
• Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s)
• History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
• Known history of human immunodeficiency virus (HIV) infection
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers
• Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
• Prior allogeneic stem cell transplantation or organ transplantation
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
• Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
• Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
• Inability to swallow capsules or disease significantly affecting gastrointestinal function
• Pregnant or breastfeeding woman NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.