SYST-13 PHASE II STUDY OF THE COMBINATION OF LIPOSOMAL IRINOTECAN AND PEMBROLIZUMAB FOR TRIPLE-NEGATIVE BREAST CANCER (TNBC) WITH BRAIN METASTASES (BM)

Abstract BACKGROUND Breast cancer is one of the most common cancers associated with brain metastases (BM). Up to 50% patients metastatic triple-negative breast (TNBC) develop BM which portends a poor prognosis, median survival 4.4-7.3 months. There lack effective systemic therapy. Irinotecan topoisomerase-1 inhibitor response rate 5-23% in advanced cancer. Nal-IRI an intravenous liposomal formulation irinotecan, greater efficacy tumor growth inhibition and ability cross blood barrier (BBB) than resulting prolonged preclinical TNBC models. Additionally, has demonstrated promising anti-tumor activity TNBC- phase-I trial (NCT01770353). Pembrolizumab humanized anti-PD-1 monoclonal antibody shown TNBC. The purpose this study evaluate whether combination pembrolizumab can provide synergic effect control CNS disease prolong progressive BM. METHODS This phase II, single arm safety lead-in nal-IRI (50-70mg/m2 IV Q2W) (400mg Q6W). Simon’s 2-stage design used, 18 1st stage additional 24 at 2nd for total 42. first 6 will serve as lead-in. Key eligibilities include: histologically/cytologically confirmed new or BM; prior immunotherapy allowed but not nal-IRI/irinotecan; sacituzumab-govitecan permitted if stable ≥16-week while on therapy ≥24-week washout starting trial; measurable disease; ≤4 lines setting. primary endpoint (DCR) months using RANO-BM criteria. Secondary endpoints include non-CNS ORR, PFS OS. (ClinicalTrials.gov: NCT05255666)