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)

Conditions: Metastatic Breast Cancer

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 subjects in the three cohorts will be treated until disease progression, intolerable toxicity, informed consent withdrawn, or investigators-determined medication termination.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

Eligibility criteria:
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.

Keywords: triple negative breast cancer