MCLA-128 Science - Merus NRG1 Clinical Trial

Clinical trials are ongoing for cancer patients who have solid tumors that have a specific genetic abnormality called an NRG1 Fusion.

NRG1 Fusion: The Science Behind Zenocutuzumab (MCLA-128)

NRG1 Fusions

Different types of cancer can sometimes be distinguished by changes to certain genes. Tumors with certain abnormal changes to a gene may respond differently to cancer treatments.

Certain kinds of alterations in the NRG1 gene are called NRG1 Fusions and may cause increased levels of the growth factor NRG1, which is capable of leading to activation of tumor growth. NRG1 Fusions have been identified in patients with different types of solid tumors, including non-small cell lung cancer (NSCLC), pancreatic cancer, gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer.

Source: Cell Volume 33, Issue 5, May 2018

About MCLA-128

Zenocutuzumab (MCLA-128) is an experimental medicine that is believed to work by blocking the action of the growth factor NRG1 – a protein that can be overproduced due to NRG1 Fusions – and prohibiting it from binding to HER3. HER3 is a protein that sits on the surface of cancer cells, which when it combines with a second surface protein HER2, it sends signals to drive tumor growth and survival. NRG1 induces the combination of HER2 and HER3.

Geuijen et al. (2018) Cancer Cell

Zenocutuzumab (MCLA-128) is a bispecific antibody, which means it is able to recognize two different proteins, specifically HER2 and HER3. Zenocutuzumab (MCLA-128) is designed to have a ‘dock and block’ mechanism:

First, zenocutuzumab (MCLA-128) docks onto HER2.
Then, it is able to block HER3’s ability to bind NRG1.

When zenocutuzumab (MCLA-128) interacts with HER2 and HER3, in preclinical models it has been shown that the growth and survival signal driving NRG1 fusion cancer progression is disrupted.
In addition to its direct action on the cancer cell linking to HER2 and HER3, zenocutuzumab (MCLA-128) is manufactured in a way that aims to increase a patient’s own ability to attack cancer, called antibody-dependent cell-mediated cytotoxicity (ADCC) properties. Zenocutuzumab (MCLA-128) is designed to have enhanced ADCC activity.