FDA grants accelerated designation to new TKK1 therapy for ER+/HER2- advanced breast cancer

The investigational drug, CFI-402257, has attracted FDA attention for 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-positive (ER)-negative/HER2-negative advanced breast cancer after disease progression on prior CDK4/6 inhibitors and endocrine therapy, either as monotherapy and in combination with fulvestrant.1

CFI-402257 is an HPK1 inhibitor that, in preclinical research, has been found to be a therapeutic strategy for patients with ER-positive breast cancer who develop resistance to CDK4/6 inhibitors.1.2 The agent is now being evaluated in a Phase 1 dose confirmatory study (NCT05251714).3

“There is an urgent need for new, safe and effective therapies to treat ER+/HER2- breast cancer, particularly when standard-of-care regimens fail,” said Mark Bray, PhD, Chief Security Officer and co-founder by Treadwell, in a press release. “CFI-402257 showed early signs of durable activity with a manageable safety profile, as monotherapy and in combination with fulvestrant in patients with ER+/HER2- breast cancer who have failed CDK4/6 inhibitors. We are grateful for the accelerated 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 a once-daily oral dose of CFI-402257 for a cycle of 28 in dose escalation part A and – phase of expansion. Those in Part B of the dose escalation and expansion phase will be given a once-daily oral dose of CFI-402257 for a 28-day cycle in combination with fulvestrant 500 mg given on day 1 and day 15 of cycle 1 and on day 1 of each subsequent cycle.

As co-primary endpoints, the study is evaluating the incidence of adverse events in the monotherapy arm and the combination arm. 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 variant allele function.

Patients eligible for study enrollment are those with histologically or cytologically confirmed advanced cancer that has progressed on at least 1 prior line of systemic therapy, measurable or unmeasurable disease per RECIST 1.1 guidelines, adequate laboratory testing at baseline , a

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

The study excludes patients who received chemotherapy, biologic therapy, or investigational treatment less than 4 weeks prior to the start of the study. Also excluded are those who are growth factor within 14 days prior to initiation of CFI-402257 administration and those who underwent major surgery within 21 days of initiation of therapy. Patients with active infections, central nervous system involvement, or other comorbidities that may interfere with the safety and efficacy of CFI-402257 will also be excluded.

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


1. Treadwell Therapeutics announces accelerated designation granted by the FDA to CFI-402257 for the treatment of ER+/HER2- breast cancer. Treadwell Therapeutics. Press 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. Ski 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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