Primary Objectives~To evaluate the safety and tolerability of selinexor in combination with nivolumab and ipilimumab~To determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of selinexor in combination with nivolumab and ipilimumab in patients with advanced or metastatic solid tumor malignancies.~Secondary Objectives~To determine Selinexor pharmacokinetics (PK) in Asian patients~To describe anti-tumor responses with the combination in patients with advanced or metastatic solid tumor malignancies.~Exploratory Objectives~To assess the immunomodulatory effects of selinexor in solid tumour malignancies and circulating immune cells~To identify biomarkers of response to the combination of selinexor and nivolumab + ipilimumab. We will explore changes in PDL1 expression, T cell infiltration (including CD4 and CD8 positive cells), gene expression profiles on serial tumor biopsies pre-selinexor, post-selinexor alone, and after the combination of selinexor and ipilimumab + nivolumab where feasible.
This is a single-centre, phase 1a (dose escalation) and 1b (dose expansion) study to evaluate the safety and tolerability of oral Selinexor in combination with nivolumab and ipilimumab in patients with advanced solid malignancies.