Treadwell Therapeutics announced the initiation of three expansion cohorts in its ongoing Phase 1 study evaluating CFI-402257, a selective and highly potent oral inhibitor of tyrosine threonine kinase (TTK).

The expansion cohorts include ER+/HER2 breast cancer patients in combination with fulvestrant post CDK4/6 inhibitor failure, triple negative breast cancer patients and an additional cohort in solid tumors.

“CFI-402257 is a potentially best-in-class, highly selective and potent inhibitor of TTK, a critical component of the cancer cell’s maintenance of genomic integrity and survival, which may be a key vulnerability of tumors that are resistant to CDK4/6 inhibitors,” said Dr. Mark Bray, Treadwell Chief Scientific Officer and Co-Founder. “We are very encouraged by the compelling early signs of clinical activity of CFI-402257 as a monotherapy in the dose escalation portion of our Phase 1 study, and we look forward to continuing to evaluate the potential of our TTK inhibitor in combination therapy through our expansion cohorts.”

“Patients with ER+/Her2- breast cancer face a high unmet medical need, as a majority of these patients become resistant to CDK4/6 inhibitors. We are very pleased by the initial indications of clinical activity in this patient segment and are excited to advance to the next phase of the study to evaluate the potential of CFI-402257 as a treatment for these patients,” said Philippe Bedard, M.D., Princess Margaret Cancer Centre, primary investigator of the study.

The open-label Phase 1 trial of CFI-402257 is designed to assess the safety, tolerability, pharmacokinetics, and clinical benefit of treatment with CFI-402257. The study consists of two parts, the dose escalation portion, now completed, in which escalating doses were administered orally in patients with advanced cancer that was refractory to current treatment or for which no curative therapy exists. The dose expansion portion of the multi-center trial will enroll up to 52 patients across sites in Canada in three parallel arms: patients with ER+/HER2-negative breast cancer who have failed CDK4/6 inhibitors in combination with an approved endocrine treatment (fulvestrant); patients with triple negative breast cancer (TNBC); and patients with advanced solid tumors. Dr. Philippe Bedard of the Princess Margaret Cancer Centre is the primary investigator, and Dr. John Hilton (Ottawa Hospital Cancer Center) and Dr. Daniel Renouf (British Columbia Cancer Agency) are co-investigators of the study.

CFI-402257 is a potentially best-in-class inhibitor of TTK protein kinase. TTK is a dual-specificity serine-threonine kinase that is critical for the spindle assembly checkpoint (SAC), chromosome alignment and error correction. Inhibition of TTK kinase activity causes cells to prematurely exit mitosis with unattached chromosomes, resulting in severe chromosome missegregation, aneuploidy and eventually cell death. TTK is overexpressed in several tumors, and higher levels correlate with worse prognosis, and may contribute to the survival and proliferation of aneuploid cells. During initial preclinical screening studies, CFI-402257 demonstrated a desirable combination of potent inhibition of cancer cell growth and high oral bioavailability with robust suppression of tumour growth achieved upon at tolerated doses in in vivo studies.