FDA Fast-Tracks ETX-636 in PIK3CA-Mutant, HR+ Breast Cancer

The FDA has granted fast track designation to ETX-636, a pan mutant-specific allosteric PIK3CA inhibitor, for the treatment of patients with PIK3CA-mutant, hormone receptor (HR)-positive (+), HER2-negative (–) advanced breast cancer.¹

FDA fast track is a process intended to facilitate the development and expedite the review of drugs that treat serious conditions and fill unmet medical needs.² This is determined by whether the drug will have an impact on survival or day-to-day function or can slow the progression of a disease to a more serious state. Drugs that receive fast track designation are eligible for more frequent meetings with the FDA, more frequent written communication from the FDA, eligibility for accelerated approval and priority review if relevant criteria are met, and rolling review.

"Patients with advanced HR+/HER2– breast cancer harboring PIK3CA mutations have poor prognosis, and there is an unmet need for therapies targeting this population that are safer and more efficacious than the current FDA approved non-mutant selective treatments," said Shengfang Jin, MD, CEO and co-founder of Ensem Therapeutics, in a press release. "We are appreciative that the FDA has recognized ETX-636 as a potentially important treatment for this indication and we remain laser-focused on demonstrating its benefit to patients in our current clinical trials."

A phase 1/2 first-in-human study (NCT06993844) is assessing ETX-636 in patients with solid tumors harboring a PIK3CA mutation.³ The primary end points are safety, tolerability, and efficacy per overall response rate. Secondary end points include pharmacokinetics, changes in fasting blood glucose, clinical benefit rate, time to response, duration of response, and disease control rate.

Patients with advanced breast cancer are included in the part B dose-escalation arm and part C dose-expansion arms of the study. In part B, ETX-636 will be administered orally in escalating dose levels in combination with a fixed dose of fulvestrant (Faslodex). In part C, select dose levels of ETX-636 will be expanded with the same fixed dose of fulvestrant.

Patients are required to have at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function. Those with breast cancer must have confirmed metastatic or locally advanced HR+/HER2– disease not amenable to surgical resection and have received at least 1 prior CDK4/6 inhibitor and at least 1 prior antiestrogen therapy. Those with symptomatic brain or spinal metastases, established diagnosis of diabetes mellitus type 1 or uncontrolled diabetes mellitus type 2, or have toxicities from previous anticancer treatments that have not resolved are not eligible to participate in the study.

The study is recruiting patients at 6 sites in California, North Carolina, Texas, and Virginia, with an estimated enrollment of 233. The estimated study completion date is December 30, 2027.

REFERENCES:

1. Ensem Therapeutics Announces ETX-636 Granted Fast Track Designation by the FDA for Advanced Breast Cancer. News release. Ensem Therapeutics. October 1, 2025. Accessed October 2, 2025. https://tinyurl.com/3jurez4d

2. Fast Track. US FDA. Updated August 13, 2024. Accessed October 2, 2025. https://tinyurl.com/y748ywj9

3. Phase 1/​2 Study of ETX-636 in Participants With Advanced Solid Tumors. ClinicalTrials.gov. Updated September 17, 2025. Accessed October 2, 2025. https://www.clinicaltrials.gov/study/NCT06993844