Title

First-in-human study of REGN3767 (R3767), a human LAG-3 monoclonal antibody (mAb), ± cemiplimab in patients (pts) with advanced malignancies

Document Type

Conference Proceeding

Publication Date

10-2019

Publication Title

J Clin Oncol

Abstract

Background: We present initial safety, pharmacokinetics (PK), and efficacy from the dose escalation study of R3767, alone (mono) or in combination with cemiplimab (REGN2810), a PD-1 mAb (combo), in pts with advanced malignancies (NCT03005782). Methods: Pts who had progressed on prior therapy(ies) and/or for whom no therapy with clinical benefit was available were enrolled; most pts had received no prior anti-PD-1/PD-L1. Pts received R3767 1, 3, 10, or 20 mg/kg every 3 weeks (Q3W) ± cemiplimab 3 mg/kg or 350 mg Q3W IV for ≤51 weeks. Crossover from mono to combo was allowed at progression. R3767 PK were evaluated. Tumor measurements were performed Q6W for the first 24 weeks and subsequently Q9W. Data cut-off date was Aug 25, 2018. Results: Mono: 27 pts (median age: 66 yr; ECOG PS: 0 [n=4], 1 [n=23]) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was nausea (22.2%). Grade ≥3 immune-related adverse events (irAEs) of increased alanine and aspartate aminotransferases (each 3.7%) were reported. By investigator-assessment (per RECIST 1.1; INV), best response was stable disease in 11 pts. Combo: 42 pts (median age: 60 yr; ECOG PS: 0 [n=15], 1 [n=27]) were treated. One pt treated with R3767 3 mg/kg Q3W + cemiplimab 3 mg/kg Q3W experienced DLT of grade 4 elevated blood creatine phosphokinase, associated with grade 3 myasthenia syndrome and grade 1 elevated troponin. The most common TEAEs were fatigue (33.3%) and nausea (21.4%). Grade 3 irAE of hypothyroidism (2.4%) was also reported. By INV, 2 (both small cell lung cancer) combo pts and 2 (endometrial cancer and cutaneous squamous cell carcinoma) of 12 additional pts who crossed over from mono to combo had partial responses. PK: R3767 concentrations in serum increased in a dose-dependent manner and were unaffected by combo. Conclusions: The safety profile of R3767 ± cemiplimab was generally tolerable; PK was linear. Early efficacy signals were detected despite the difficult-to-treat pt population. Biomarker studies are ongoing. R3767 20 mg/kg or 1600 mg fixed dose equivalent Q3W as mono and combo were selected for further evaluation.

Volume

37

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