A study of REGN3767, an antiLAG3 antibody, alone and in combination with cemiplimab (REGN2810), an antiPD1 antibody in advanced cancers
Papadopoulos KP, Lakhani N, Johnson ML, Park H, Wang D, Yap TA, Moore KN, Sims TN, Emeremni CA, Karasarides M, and Kroog GS. A study of REGN3767, an antiLAG3 antibody, alone and in combination with cemiplimab (REGN2810), an antiPD1 antibody in advanced cancers. J Clin Oncol 2019; 37.
J Clin Oncol
Background: Lymphocyte activation gene 3 (LAG3) is an immune checkpoint receptor with a biological role in Tcell regulation. Analysis of immunecell infiltrates from human tumors show that a subset of CD4+ and/or CD8+ cells coexpress LAG3 and PD1 and may be associated with decreased Tcell effector function and tumor escape (Baitsch, 2011; Jie, 2013). Preclinical models provide evidence that dual inhibition of LAG3 and PD1 blockade offer synergistic antitumor 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 tumorspecific expansion cohorts. Solid tumor expansion cohorts will enroll per Simon's twostage design to evaluate safety and preliminary efficacy. Lymphoma expansion cohorts will enroll 15 patients. Patients who are antiPD1/PDL1 therapy naïve and experienced are eligible for separate cohorts. Patients previously exposed to antiLAG3 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 antitumor efficacy in dose escalation, and safety in dose expansion. This trial is actively enrolling eligible patients in the US, UK, Ireland, and South Korea.