Hypothesis The investigators hypothesize that the combination of Talazoparib and Selinexor will have clinical efficacy in TNBC, independent of BRCA mutation status.~Primary Objectives~To determine the safety profile of combination of Talazoparib and Selinexor in advanced/ metastatic solid tumors.~To determine the RP2D of Talazoparib and Selinexor combination therapy in patients with advanced/ metastatic solid tumors.~Secondary Objectives~• To determine the objective response rate to combination Talazoparib and Selinexor in advanced/ metastatic TNBCs.~Exploratory Objectives~To assess the effect of the combination on pharmacokinetics of Talazoparib and Selinexor~To explore the impact of pharmacogenetics on toxicity and efficacy of combination Talazoparib and Selinexor.~To assess changes in circulating tumor cells and plasma biomarkers during treatment.~To assess pharmacodynamic changes and predictive biomarkers in tumor tissue during treatment.
This is a single arm, open-label, phase I dose finding study, followed by a phase II expansion study. Phase I will be carried out in a modified 3+3 dose escalation design, with a projected enrolment of 33 patients with refractory solid tumors to determine the RP2D. In the phase II portion, a total of 30 patients with advanced/metastatic TNBC will be enrolled.