Author: Alex Biese

The first patent has been dosed in a clinical trial evaluating a new treatment for breast cancer and other solid tumors.

Work is underway on a phase 1/2 trial evaluating STX-478 — an oral drug that can penetrate into the central nervous system (CNS) and inhibit mutant phosphoinositide-3-kinase alpha (PI3Kα) — as a monotherapy for tumors including breast and gynecological cancers and head and neck squamous cell carcinoma (HNSCC), as well as a monotherapy and in combination with approved agents in patients with HR+/HER2- breast cancer, according to a May 2 news release from Scorpion Therapeutics, Inc., the manufacturer behind the novel drug.

With approximately 160 participants, all 18 or older with advanced solid tumors, the study launched in April. It is expected to be completed by June 2026, with the aim of evaluating the safety, tolerability, pharmacokinetics (the activity of drugs in the body) and preliminary antitumor activity of STX-478.

The trial, per the announcement from Scorpion, is working to determine the safety profile of STX-478 and establish a maximum tolerated does as well as a lower optimal-biologically active dose, if appropriate, as a recommended phase 2 dose as a monotherapy for breast cancer and other solid tumor types, as well as a combination agent in PI3Kα-mutant HR+/HER-2- breast cancer.

Scorpion plans to then evaluate STX-478 as a monotherapy treatment for patients with solid tumors with PI3Kα-mutations including breast cancer, gynecological cancers, HNSCC and gastrointestinal cancers. Secondary trial objectives include evaluating the pharmacokinetic profile, pharmacodynamic effects (how it works in the body) and clinical response.

STX-478, Scorpion explained in the press release, has been designed for patents with tumors featuring prevalent PI3Kα mutations, which occur in more than 166,000 patients with breast, gynecological and head and neck cancers in the United States each year.

Current treatments for PI3Kα-mutated cancers inhibit the normal, or wild-type, version of PI3Kα in healthy tissues, potentially leading to side effects including hyperglycemia (high blood sugar) and rash, according to the news release, which limits patients’ long-term tolerance of the treatments. The treatments, Scorpion noted, have “little to no CNS penetrance, despite the fact that up to 50% of all solid tumor patients develop significant morbidity and mortality from brain metastases.”

“STX-478 is a wild-type-sparing, CNS-penetrant, oral inhibitor of mutant PI3Kα with excellent pre-clinical pharmacokinetic properties,” Dr. Michael Streit, chief medical officer of Scorpion, said in the news release. “In this Phase 1/2 trial, we will aim to demonstrate how these important traits translate into a potentially superior product profile that offers a wider therapeutic window and greater efficacy.

“We anticipate presenting initial safety, pharmacokinetic and pharmacodynamic results in 2024, including data on STX-478’s impact on potential biomarkers suggestive of anti-tumor activity. We believe these initial data could differentiate STX-478 from existing agents currently on the market or in development, and support its profile as a safe and highly differentiated therapeutic for the treatment of solid tumors, especially HR+/HER2- breast cancer. We look forward to partnering with study investigators to evaluate STX-478 in patients with PI3Kα-mutated cancers.”