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.

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

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	1	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
CD274 positive	lung adenocarcinoma	no benefit	LMB-100	Preclinical - Cell culture	Actionable	In a preclinical study, a CD274 (PD-L1) positive mouse lung adenocarcinoma cell line was not sensitive to treatment with LMB-100 in culture (PMID: 32611684).	32611684
CD274 positive	malignant mesothelioma	predicted - sensitive	Pembrolizumab	Clinical Study	Actionable	In a clinical study, 80% (4/5) of MSLN positive mesothelioma patients with CD274 (PD-L1) expression who had progressed on LMB-100 demonstrated an objective response when treated with Keytruda (pembrolizumab), and compared to patients without CD274 expression (n=5), treatment significantly prolonged median progression-free survival (11.3 vs 2.1 mos, p<0.0018) but not overall survival (27.2 vs 6.8 mos, p=0.1) (PMID: 32611684).	32611684