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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



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