Please login to the form below

Not currently logged in

Merus makes case for bispecific antibody in specific cancer gene fusion

Could become a potential treatment for hard-to-treat cancers


Merus, a Dutch biotech developing full-length bispecific antibodies, has presented early clinical data of its lead candidate in cancers with NRG1 gene fusions.

The experimental drug, named MCLA-128, was studied in three patients via an early access programme. These patients had cancers which carried NRG1 fusions, which are present in several cancer types, but lack significant treatment options.

When this particular gene fusion protein is present in a tumour, it increases growth by binding to HER3 receptors on the cell surface, which then recruit HER2. When both HER2/HER3 combine, this activaes a signalling pathway that is crucial for cancer survival and causes cancer proliferation.

MCLA-128 operates in two arms – firstly, one arm docks the drug on HER2, which impairs the ability of both receptors to cooperate. The other binds to HER3 at the NRG1 binding site, which in turn prevents these fusions from activating HER3.

The initial data showed that patients who were treated with MCLA-128, at 750mg administered intravenously every other week, experienced tumour shrinkage, symptomatic improvement and durability up to their most recent assessment. The three patients are currently remaining on treatment.

The data also showed that the experimental therapy worked across cancer types – patient one and two had pancreatic ductal adenocarcinoma, with the third patient suffering from non-small cell lung cancer. Imaging at eight weeks showed a respective 44%, 22% and 33% reduction in tumour diameter for the individual patents.

“These initial data are an important proof-of-concept demonstrating the promise of targeting NRG1 fusions with MCLA-128,” said Alison Schram, a medical oncologist in the Early Drug Development Service at MSKCC, and investigator for the three patients.

“It is notable that two of the patients described have pancreatic cancer, a disease with a poor prognosis and limited therapeutic options. MCLA-128’s mechanism of action addresses the specific molecular abnormality in cancers harbouring NRG1 fusions by binding to HER2 and blocking the interaction of the NRG1 fusion oncoprotein with HER3, and may make MCLA-128 uniquely suited to target this distinct oncogenic driver,”she added.

Merus is currently evaluating MCLA-128 in both an ongoing phase 1/2 trial in patients with NRG1 fusions and a phase 2 trial in patients with metastatic breast cancer.

Article by
Lucy Parsons

28th October 2019

From: Research



COVID-19 Updates and Daily News

Featured jobs


Add my company

Iguazu Ltd is a digital healthcare agency, delivering tactical and innovative solutions. WHAT WE DO We are Closed Loop Marketing...

Latest intelligence

Avoiding A Series of Unfortunate Events: launch lessons from lockdown
Chris Ross takes a novel look at launch excellence through the lens of COVID-19 and explores how pharma’s launch leaders are rewriting the story...
6 reasons patients drop out of clinical trials and 6 ways to fix it
If you’ve successfully recruited patients for your clinical trial, but one by one, they begin to drop out, then this information could be for you....
Sharing patient stories for World Pulmonary Hypertension Day
For World Pulmonary Hypertension Day and we’re here to help raise awareness of pulmonary hypertension (PH) - a frequently under and misdiagnosed condition. Created in collaboration with the PH patient...