Reference Detail

Ref Type

Journal Article

PMID

(32611684)

Authors

Jiang Q, Ghafoor A, Mian I, Rathkey D, Thomas A, Alewine C, Sengupta M, Ahlman MA, Zhang J, Morrow B, Steinberg SM, Pastan I, Hassan R

Title

Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti-PD-1 antibody in patients with mesothelioma and mouse tumor models.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Science translational medicine	12	550	2020 Jul 01		Sci Transl Med

URL

Abstract Text

LMB-100 is an immunotoxin targeting the cell surface protein mesothelin, which is highly expressed in many cancers including mesothelioma. Having observed that patients receiving pembrolizumab off protocol after LMB-100 treatment had increased tumor responses; we characterized these responses and developed animal models to study whether LMB-100 made tumors more responsive to antibodies blocking programmed cell death protein 1 (PD-1). The overall objective tumor response in the 10 patients who received PD-1 inhibitor (pembrolizumab, 9; nivolumab, 1) after progression on LMB-100 was 40%, and the median overall survival was 11.9 months. Of the seven evaluable patients, four had objective tumor responses, including one complete response and three partial responses, and the overall survival for these patients was 39.0+, 27.7, 32.6+, and 13.8 months. When stratified with regard to programmed death ligand 1 (PD-L1) expression, four of five patients with tumor PD-L1 expression had objective tumor response. Patients with positive tumor PD-L1 expression also had increased progression-free survival (11.3 versus 2.1 months, P = 0.0018) compared with those lacking PD-L1 expression. There was no statistically significant difference in overall survival (27.7 versus 6.8 months, P = 0.1). LMB-100 caused a systemic inflammatory response and recruitment of CD8+ T cells in patients' tumors. The enhanced antitumor effects with LMB-100 plus anti-PD-1 antibody were also observed in a human peripheral blood mononuclear cell-engrafted mesothelioma mouse model and a human mesothelin-expressing syngeneic lung adenocarcinoma mouse model. LMB-100 plus pembrolizumab is now being evaluated in a prospective clinical trial for patients with mesothelioma.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
LMB-100	LMB-100	0	3

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
LMB-100		RG7787\|RO-6927005\|RO6927005\|LMB100		LMB-100 is an immunotoxin that targets mesothelin, potentially resulting in antitumor activity (PMID: 27863199, PMID: 32611684).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References