Reference Detail

Ref Type

Journal Article

PMID

(27216193)

Authors

Moores SL, Chiu ML, Bushey BS, Chevalier K, Luistro L, Dorn K, Brezski RJ, Haytko P, Kelly T, Wu SJ, Martin PL, Neijssen J, Parren PW, Schuurman J, Attar RM, Laquerre S, Lorenzi MV, Anderson GM

Title

A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer research	76	13	2016 Jul 01	3942-53	Cancer Res

URL

Abstract Text

Non-small cell lung cancers (NSCLC) with activating EGFR mutations become resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M) and/or activation of the cMet pathway. We engineered a bispecific EGFR-cMet antibody (JNJ-61186372) with multiple mechanisms of action to inhibit primary/secondary EGFR mutations and the cMet pathway. JNJ-61186372 blocked ligand-induced phosphorylation of EGFR and cMet and inhibited phospho-ERK and phospho-AKT more potently than the combination of single receptor-binding antibodies. In NSCLC tumor models driven by EGFR and/or cMet, JNJ-61186372 treatment resulted in tumor regression through inhibition of signaling/receptor downmodulation and Fc-driven effector interactions. Complete and durable regression of human lung xenograft tumors was observed with the combination of JNJ-61186372 and a third-generation EGFR TKI. Interestingly, treatment of cynomolgus monkeys with JNJ-61186372 resulted in no major toxicities, including absence of skin rash observed with other EGFR-directed agents. These results highlight the differentiated potential of JNJ-61186372 to inhibit the spectrum of mutations driving EGFR TKI resistance in NSCLC. Cancer Res; 76(13); 3942-53. ©2016 AACR.

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
Amivantamab-vmjw	Amivantamab-vmjw	0	8

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Amivantamab-vmjw	Rybrevant	JNJ-61186372	EGFR Antibody 56 MET Antibody 28	Rybrevant (amivantamab-vmjw) is a bi-specific antibody that targets EGFR and MET, resulting in inhibition of downstream signaling and potentially leading to decreased growth of EGFR and/or MET-expressing tumors (PMID: 27216193, PMID: 32414908). Rybrevant (amivantamab-vmjw) is FDA approved for use in patients with locally advanced or metastatic non-small cell lung cancer harboring EGFR exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy (FDA.gov).

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