In a recent discussion with CancerNetwork®, Dr. Alberto J. Montero highlighted positive efficacy and safety data from a phase 1 trial (NCT05768139) of STX-478, a mutant-selective PI3Kα inhibitor being evaluated for PI3K-mutated advanced solid tumors. Results presented at the 2024 European Society for Medical Oncology Congress (ESMO) indicated an overall response rate of 21% across all tumor types, with higher efficacy in breast cancer (23%) and gynecologic tumors (44%). Importantly, the treatment minimized common PI3K inhibitor-related toxicities such as hyperglycemia, diarrhea, and rash, which are often seen with other PI3K inhibitors like alpelisib.

Dr. Montero emphasized that the trial demonstrated clinical activity across PI3Kα mutations and showed that STX-478 was well-tolerated with a maximally tolerated dose of 100 mg. Unlike traditional PI3K inhibitors, STX-478 caused no severe metabolic toxicities, though mild fatigue was noted. These findings underscore STX-478’s potential as a more tolerable PI3K-targeted therapy, especially promising for cancers with PI3K pathway involvement.

In prostate cancer, PI3K mutations can play a role in resistance to treatment and disease progression, making advancements like STX-478 valuable for future prostate cancer research.

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