FDA Grants Fast Track Designation to Novel TKK1 Therapy for ER+/HER2- Advanced Breast Cancer

The investigational drug, CFI-402257, has earned the FDA’s attention for promising preclinical results, and is now under investigation in a phase 1 study.

The FDA has granted fast track designation to CFI-402257for the treatment of adult patients with estrogen receptor (ER)-positive/HER2-negative advanced breast cancer after disease progression on prior CDK4/6 inhibitors and endocrine therapy, both as a monotherapy and in combination with fulvestrant.1

CFI-402257 is a HPK1 inhibitor that, in preclinical research, was found to be a therapeutic strategy for ER-positive breast cancer patients who develop resistance to CDK4/6 inhibitors.1,2 The agent is now being evaluated in a phase 1 dose-confirming study (NCT05251714).3

"There is an urgent need for new, safe and efficacious therapies to treat ER+/HER2- breast cancer, particularly when standard of care regimens fail," said Mark Bray, PhD, Treadwell chief security officer and co-founder, in a press release. "CFI-402257 has shown early signs of durable activity with a manageable safety profile, as a monotherapy and in combination with fulvestrant in ER+/HER2- breast cancer patients that have failed CDK4/6 inhibitors. We are thankful for the fast track designation granted by the FDA and look forward to the continued development of CFI-402257 in ER+/HER2- breast cancer."

In the phase 1 study of CFI-402257, up to 44 patients with ER-positive/HER2-negative advanced breast cancer will receive an oral once daily dose of CFI-402257 for a 28-cycle in the part A dose-escalation and -expansion phase. Those in the part B dose-escalation and -expansion phase will be administered an oral once daily dose of CFI-402257 for a 28-day cycle in combination with fulvestrant 500 mg administered on day 1 and day 15 of cycle 1 and day 1 of each subsequent cycle.

As co-primary end points, the study is evaluating the incidence of adverse events in the monotherapy arm and combination arm. The secondary end points of the study include objective response rate, objective response rate in the combination arm, pharmacokinetics, and the effect of CFI-402257 treatment on changes in variant allele function.

Patients eligible to enroll in the study are those with a histological or cytological confirmation of advanced cancer that has progressed on at least 1 prior line of systemic therapy, measurable or non-measurable disease as per RECIST 1.1 guidelines, adequate laboratory tests at baseline, an

ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. Patients are required to have the ability to swallow oral medications and use contraception during the study. Female patients are required to produce a negative pregnancy test before being treated in the study.

The study excludes patients who have received chemotherapy, biological therapy, or investigational treatment less than 4 weeks before the start of the study. In addition, those who are growth factors within 14 days prior to initiation of dosing of CFI-402257 and those who have had major surgery within 21 days of starting therapy, are excluded. Patients with active infections, central nervous system involvement or other comorbidities that may interfere with the safety and effectiveness of CFI-402257 will also be excluded.

Individuals who meet the inclusion criteria are being recruited at study sites in Ohio, Texas, and Utah.


1. Treadwell Therapeutics announces fast track designation granted by the FDA to CFI-402257 for the treatment of ER+/HER2- breast cancer. Treadwell Therapeutics. News release. January 10, 2023. Accessed January 10, 2023. https://yhoo.it/3X0rcQz

2. Soria-Bretones I, Thu KL, Silvester J, et al. The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER+ breast cancer with mitotic aberrations. Sci Adv. 2022 Sep 9;8(36):eabq4293. doi:10.1126/sciadv.abq4293.

3. CFI-402257, a potent and selective TTK Inhibitor, in solid tumors and with fulvestrant in breast cancer. ClinicalTrials.gov. Updated July 29, 2022. Accessed January 10, 2023.