Release Date: 17-Jul-2024
Merus developed MCLA-158 (Petosemtamab), a Biclonics bispecific antibody targeting EGFR and LGR5 for the treatment of solid tumors characterized by EGFR and LGR5 overexpression. MCLA-158, as a first-in-class candidate targeting of EGFR and LGR5, is setting a new standard and highlighting the unique approach to treating cancer at its molecular foundations.
EGFR, a cell surface receptor, and LGR5, a stem cell marker, both play important roles in cancer progression. Overexpression of EGFR is frequently associated with uncontrolled cell proliferation, which is a hallmark of cancer. LGR5, being a stem cell marker, has been linked to tumor initiation and maintenance, as well as tumor recurrence, therapeutic resistance, and distant metastasis. By targeting both of these proteins, MCLA-158 offers a dual-action method to address the diverse characteristics of cancer, aiming for a more comprehensive and successful treatment.
The cancer mechanism of MCLA-158 is precision personified. According to researchers at the Institute for Research in Biomedicine in Barcelona, MCLA-158 degrades the EGFR protein in cancer stem cells expressing the LGR5 marker, hence inhibiting the growth and survival pathways in the cells that originate and propagate cancer. This antibody, however, has no effect on the function of healthy stem cells, which are required for tissue function.
MCLA-158’s progression from development to phase I/II trials highlights its potential significance in treating advanced solid tumors, including metastatic colorectal cancer. It’s currently in an expansion phase study, showing promising clinical performance and manageable safety in pretreated gastric adenocarcinoma and head and neck squamous cell cancer (HNSCC) patients, without dose-limiting toxicities reported.
As a result, the introduction of MCLA-158 into the pharmaceutical market has the potential to change the cancer treatment landscape. With interim data from the current trial indicating consistent and clinically relevant action of MCLA-158 in patients with previously treated solid tumors, clinical validation for this first-of-its-kind EGFR and LGR5 targeting therapeutic is slowly being reached. Additionally, Fast Track Designation from the FDA in May 2024 for HNSCC further highlights its therapeutic promise.
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