The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.
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Patients with metastatic colorectal cancer who have the KRAS G12C mutation demonstrated improved quality of life following sotorasib and panitumumab compared with standard therapy.
Hookipa Pharma Inc.’s nearly $1 billion collaboration with Roche Holding AG dissolved along with 30% of the company’s staff. The New York-based company said Roche ended the October 2022 deal involving the HB-700 program in treating KRAS mutated cancers but did not say why the agreement fell apart.