A phase 2 clinical trial has reported encouraging results for zovegalisib (RLY-2608), a new targeted drug for advanced breast cancer. The study involved patients with HR-positive, HER2-negative metastatic breast cancer carrying PIK3CA mutations who had already progressed after standard treatments such as CDK4/6 inhibitors. Researchers found an overall response rate of 38.7%, while patients with specific PIK3CA kinase mutations achieved a higher response rate of 66.7%. Tumor shrinkage occurred in about 80.6% of patients, and the median progression-free survival reached 10.3 months.
Around 40% of HR-positive, HER2-negative breast cancers are driven by PIK3CA mutations. Current PI3K inhibitors can affect both cancerous and healthy cells, often causing severe side effects such as rashes and high blood sugar. Zovegalisib was designed as a selective inhibitor that targets mutated proteins in tumors while sparing normal cells, which may help reduce these toxicities.
The treatment combination of zovegalisib and fulvestrant was generally well tolerated. The most common side effects included hyperglycemia, nausea, and fatigue, but most were mild to moderate. Severe rashes and mouth sores—common with older drugs in this class—were rare, and only a small percentage of patients stopped treatment because of side effects. Based on these results, researchers have launched a phase 3 trial to compare this new therapy with current standard treatment.