TAT 2020: TTK Inhibitor Plus Paclitaxel in Advanced HER2-Negative Breast Cancer
Posted: Wednesday, March 18, 2020
The combination of the investigational agent CFI-402257 and weekly paclitaxel appears to be well tolerated, according to the results of a phase Ib dose-escalation study originally intended to be presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2020 in Paris (Abstract 19O). CFI-402257—a selective oral inhibitor of threonine tyrosine protein kinase (TTK)—has shown antiproliferative and cytotoxic activity as monotherapy and may enhance the antitumor activity of paclitaxel.
“Dose escalation is ongoing, and the recommended phase II dose has not yet been defined,” stated Philippe Bedard, MD, FRCPC, of Princess Margaret Cancer Centre, University of Toronto, Canada.
In this trial, 13 patients with advanced HER2-negative breast cancer received CFI-402257 combined with weekly paclitaxel in 28-day dosing cycles. The starting dose of CFI-402257 was 84 mg on a 2-day on, 5-day off schedule with paclitaxel at 80 mg/m2 on days 1, 8, and 15. Eligible patients included women previously treated with more than one nontaxane chemotherapy who were not appropriate for endocrine therapy and had adequate organ function.
The 13 study participants received a total of 39 cycles of paclitaxel with CFI-402257 at three dose levels: 84 mg, 112 mg, and 168 mg. Of the nine evaluable patients, one responded to the combination therapy.
As for safety and tolerability, the most frequent nonhematologic adverse events were alopecia (82%), diarrhea (55%), nausea (55%), fatigue (55%), vomiting (45%), sensory neuropathy (45%), headache (45%), constipation (45%), back pain (36%), and extremity pain (36%). Although one grade 4 neutropenia dose-limiting toxicity was observed at the 168-mg dose, no related serious adverse events were seen. Grade 3 and 4 hematologic adverse events included neutropenia (27%) and anemia (9%).
Disclosure: The study authors’ disclosure information can be found at esmo.org.