LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Summary

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Description

Background: Mesothelin is expressed in approximately half of all lung adenocarcinomas. LMB-100 has demonstrated anti-tumor efficacy against several mesothelin expressing tumor models including non-small cell lung cancer (NSCLC).- Programmed death ligand 1 (PD-1) is an Ig superfamily member related t...

Background: Mesothelin is expressed in approximately half of all lung adenocarcinomas. LMB-100 has demonstrated anti-tumor efficacy against several mesothelin expressing tumor models including non-small cell lung cancer (NSCLC).- Programmed death ligand 1 (PD-1) is an Ig superfamily member related to CD28 and CTLA-4 that has been shown to negatively regulate antigen receptor signaling upon engagement of its ligands. Pembrolizumab, an IgG4 monoclonal antagonist antibody to PD-1, is FDA approved in the frontline for advanced non-squamous NSCLC as a single agent with high PD-L1 expression [tumor proportion score (TPS) >=50%] or in combination with platinum-based doublet chemotherapy (PD-L1 unselected). It also approved in the second-line for high PDL1 expressing tumors (TPS >=1%). Combination treatment with LMB-100 plus pembrolizumab results in greater anti-tumor efficacy in murine lung cancer model. Objectives: -To determine the objective response rate of LMB-100 followed by pembrolizumab in the treatment of subjects with mesothelin-expressing non-squamous non-small cell lung cancer (NSCLC) previously treated with immune checkpoint inhibitors. Eligibility: Histologically confirmed locally advanced or metastatic non-squamous, non-small cell lung cancer lacking an EGFR sensitizing mutation, ALK or ROS1 gene rearrangement and not amenable to potentially curative surgical resection or chemoradiation. Tumor mesothelin expression of at least 25% of tumor cells as determined by the Laboratory of Pathology at the NCI. Subjects must have at least progressed after one prior platinum-based doublet chemotherapy AND standard immune checkpoint inhibitor (ICI) with either frontline single-agent pembrolizumab, or in combination with platinum-based doublet chemotherapy, or second-line single-agent nivolumab, pembrolizumab, or atezolizumab. Age >= 18 years. Design: This is an open-label, single center phase II study of LMB-100 followed by pembrolizumab in subjects with mesothelin expressing NSCLC who have progressed on standard therapies Subjects will receive LMB-100 at the single agent MTD (140mg/kg) on days 1, 3 and 5 of a 21-day cycle for up to 2 cycles and pembrolizumab 200 mg on day 1 of cycle 3 of a 21- day cycle (or cycle 2 if disease progression is observed after 1 cycle) onwards until disease progression (on or after pembrolizumab) or intolerable toxicity for a maximum of 2 years (unless second course initiated). The total accrual ceiling for the screening will be set at 100 total patients in order to treat 23 subjects.

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