FDA approves fast track designation of new TKK1 therapy for ER+/HER2- advanced breast cancer

The investigational drug, CFI-402257, has earned the FDA’s attention due to promising preclinical results and is now being investigated in a phase 1 study.

The FDA granted fast-track designation to CFI-402257 for 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, as monotherapy and in combination with fulvestrant.1

CFI-402257 is an HPK1 inhibitor that has been shown in preclinical studies to represent 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 effective therapies to treat ER+/HER2- breast cancer, particularly when standard care regimens are failing,” said Dr. Mark Bray, chief safety officer and co-founder of Treadwell, in a press release. “CFI-402257 has shown early signs of long-term action with a tolerable safety profile, both as monotherapy and in combination with fulvestrant in patients with ER+/HER2- breast cancer in whom CDK4/6 inhibitors have failed. We are grateful for the fast-track designation granted by the FDA and we look forward to continuing the 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 dose of CFI-402257 once daily for 28 cycles in part A of the dose escalation and – expansion phase. Those in the escalation and dose expansion phase of Part B will receive an oral dose of CFI-402257 once daily for a 28-day cycle in combination with 500 mg of fulvestrant administered on days 1 and 15 of cycle 1 and on day 1 of each subsequent cycle.

As primary endpoints, the study evaluates the incidence of side effects in the monotherapy group and the combination group. Secondary endpoints 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 function of the variant allele.

Eligible patients for inclusion in the study are those with histological or cytological confirmation of advanced cancer that has progressed on at least 1 prior line of systemic therapy, measurable or non-measurable disease according to RECIST 1.1 guidelines, appropriate laboratory tests at baseline,

ECOG performance status 0 or 1 and a life expectancy of at least 3 months. Patients must be able to swallow oral medications and use contraception during the study. Patients must give a negative pregnancy test before being treated in the study.

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

Individuals meeting 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. January 10, 2023. Accessed January 10, 2023. https://yhoo.it/3X0rcQz

2. Soria-Bretones I, Thu KL, Silvester J, et al. A checkpoint of spindle assembly is the 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.

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