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 L et al. J Clin Investig. 2011;121:2350-2360; Jie HB et al. Br J Cancer. 2013;109:2629-2635.). 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 SR et al. Cancer Res. 2012;72(4): 917-927). 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 is exploring 4 escalating REGN3767 dose levels. Combination is exploring 3 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 phase 2 dose (RP2D, 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. Clinical Trial Information: NCT03005782.