Background: Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint receptor with a biological role in T-cell regulation. Analysis of immune-cell infiltrates from human tumors show that a subset of CD4+ and/or CD8+ cells co-express LAG-3 and PD-1 and may be associated with decreased T-cell effector function and tumor escape (Baitsch, 2011; Jie, 2013). Preclinical models provide evidence that dual inhibition of LAG-3 and PD-1 blockade offer synergistic anti-tumor effects and suggest a promising immunotherapy combination that warrants clinical investigation (Woo, 2012). This first in human study will evaluate the safety and efficacy of REGN3767 alone and in combination with cemiplimab in advanced malignancies. Methods: Phase 1 study enrolling patients with advanced malignancies. Dose escalation phase employs a modified 3+3 (4+3) design to assess the tolerability and pharmacokinetics (PK) of REGN3767 monotherapy and in combination with cemiplimab. Monotherapy and combination therapy are exploring multiple escalating REGN3767 dose levels. After tolerability and PK evaluation, doses of REGN3767 will be selected for monotherapy and combination therapy tumor-specific expansion cohorts. Solid tumor expansion cohorts will enroll per Simon’s two-stage design to evaluate safety and preliminary efficacy. Lymphoma expansion cohorts will enroll 15 patients. Patients who are anti-PD-1/PD-L1 therapy naïve and experienced are eligible for separate cohorts. Patients previously exposed to anti-LAG-3 therapy are not eligible. The primary objectives are the determination of the recommended dose for expansion (dose escalation) and ORR (dose expansion). Secondary objectives include characterization of PK and immunogenicity in all patients, as well as anti-tumor efficacy in dose escalation, and safety in dose expansion. This trial is actively enrolling eligible patients in the US, UK, Ireland, and South Korea. 1. Baitsch L et al. J Clin Investig. 2011;121:2350–2360. 2. Jie HB et al. Br J Cancer. 2013;109:2629–2635. 3. Woo SR et al. Cancer Res. 2012;72(4): 917–927. Clinical trial information: NCT03005782