Scorpion Therapeutics’ new oral cancer drug, STX-478, showed promising anti-tumor activity as a monotherapy in a Phase 1/2 trial, achieving an overall response rate (ORR) of 23% in breast cancer and 21% across all tumor types studied. The data were unveiled at the European Society for Medical Oncology (ESMO) Congress 2024, held 13–17 September 2024.
STX-478 is a potent, mutant-selective, allosteric PI3Kα inhibitor. The Phase 1/2 trial included patients with advanced solid tumors, including HR+/HER2- breast cancer (BC), gynecological tumors, and head and neck squamous cell cancer (HNSCC). The therapy demonstrated anti-tumor activity across these cancer types and appears to be well-tolerated in heavily pre-treated patients.
A sound safety profile to date
STX-478’s good safety profile is encouraging for its potential use in high-risk patients who have undergone multiple treatments. Scorpion’s CEO, Dr. Adam Friedman, stated, “STX-478 is a powerful PI3Kα pathway inhibitor. Our early results show it’s potentially the best in its class, with positive effects even as a single therapy, outperforming similar drugs.”
The class of mutant-selective PI3Kα inhibitors aims to overcome limitations of older, non-selective PI3K inhibitors, which often cause side effects like hyperglycemia, rash, and diarrhea. Several companies, including Relay Therapeutics and Lilly, are developing such inhibitors.
Trial details
In the trial, STX-478 was tested at doses from 20mg to 160mg daily, with a maximum tolerated dose (MTD) of 100mg daily. Its pharmacokinetic profile supports once-daily dosing, with a half-life of about 60 hours. The study included a diverse patient population: 54% were pre-diabetic or diabetic, 41% of breast cancer patients had prior PI3Kα pathway inhibitor treatment, and 97% had received a CDK4/6 inhibitor. This diversity underscores STX-478’s potential in treating patients with multiple prior therapies.
Filed Under: clinical trials, Drug Discovery, Oncology
