Found 1 Presentation For Request "Bedard"
19O - A phase Ib trial of CFI-402257 in combination with weekly paclitaxel in patients with advanced HER2-negative (HER2-) breast cancer (aBC) (ID 197)
- Philippe Bedard (Toronto, Ontario, Canada)
- Philippe Bedard (Toronto, Ontario, Canada)
- Mihaela Mates (Kingston, ON, Canada)
- Karen A. Gelmon (Vancouver, British Columbia, Canada)
- John Hilton (Ottawa, MA, Canada)
- Dongsheng Tu (Kingston, ON, Canada)
- Irene Li (Toronto, ON, Canada)
- Laleh Rastgou (Vancouver, Canada)
- Nancy Drummond-Ivars (Ottawa, Canada)
- Jackie Edwards (Kingston, ON, Canada)
- David Warr (Toronto, Canada)
- Caroline Lohrisch (Vancouver, Canada)
- Xinni Song (Ottawa, Canada)
- Amirrtha Srikanthan (Ottawa, Canada)
- Andrew Robinson (Kingston, ON, Canada)
- Linda Hagerman (Kingston, ON, Canada)
- Lesley K. Seymour (Kingston, Ontario, Canada)
- Moira Rushton (Kingston, Canada)
- David W. Cescon (Toronto, Canada)
Abstract
Background
CFI-402257 is a selective oral inhibitor of TTK protein kinase, a critical regulator of the mitotic spindle assembly checkpoint. TTK is overexpressed in breast cancer (BC); CFI-402257 has anti-proliferative and cytotoxic activity as monotherapy. Synergy has been identified between TTK inhibitors and taxanes; CFI-402257 enhances the antitumor activity of paclitaxel in BC xenograft models.
Methods
The primary objective was to establish the safety and recommended phase 2 dose (RP2D) of CFI-402257 combined with weekly paclitaxel. Patients with HER2-ve aBC with adequate organ function, PS 0-1, previously treated with > 1 non-taxane chemotherapy, not appropriate for endocrine therapy, were eligible. A 3+3 design was used with dose limiting toxicities (DLTs) assessed during cycle 1 (28 days). Starting dose CFI-402257 was 84mg on 2-day on, 5-day off schedule with paclitaxel 80mg/m2 day 1, 8, and 15. Safety assessments were performed weekly (CTCAE v5.0) and response (RECIST 1.1) every 2 cycles.
Results
13 patients received a total of 39 cycles at 3 dose levels (84mg, 112mg, 168mg). Median age was 51, 85% ER+/HER2-ve, 54% PS1, 50% ≥3 prior lines of chemotherapy, and 54% with ≥4 sites of metastatic disease. One grade 4 neutropenia DLT was seen at DL3; no related serious adverse events (AEs) were seen. The most frequent (≥30%) non-hematological AEs 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%). Grade ≥3 hematological AEs were neutropenia (27%) and anemia (9%). The overall response rate for evaluable patients was 1/9 = 11.1%.
Conclusion
CFI-402257 and paclitaxel is well tolerated. Dose escalation is ongoing and the RP2D has not yet been defined. Updated safety and efficacy data will be presented at the meeting.
Clinical trial identification
NCT03568422.
Legal entity responsible for the study
Canadian Cancer Trials Group.
Funding
This study was coordinated by the Canadian Cancer Trials Group supported by SU2C Canada - Canadian Cancer Society Breast Cancer Dream Team Research Funding (SU2C-AACR-DT-18-15), with supplemental support from the Ontario Institute for Cancer Research, through funding provided by the Government of Ontario.
Disclosure
P. Bedard: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): BMS; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Servier; Research grant/Funding (institution): PTC Therapeutics; Research grant/Funding (institution): SignalChem LifeSciences; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Zymeworks. K.A. Gelmon: Advisory/Consultancy, Research grant/Funding (institution): AZ; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Oncothyreon; Advisory/Consultancy: Nanostring; Advisory/Consultancy: Merck; Advisory/Consultancy: Mylan; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Genentech. J. Hilton: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Puma; Advisory/Consultancy: Novartis; Advisory/Consultancy, Non-remunerated activity/ies, Data Monitoring Committee: BMS; Advisory/Consultancy: AZ. L.K. Seymour: Research grant/Funding (institution), For trial costs: University Health Network. D.W. Cescon: Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Novartis; Advisory/Consultancy: AZ; Advisory/Consultancy: Roche; Advisory/Consultancy: Puma; Advisory/Consultancy: Agendia; Advisory/Consultancy: Dynamo Therapeutics; Non-remunerated activity/ies, Patent holder (to institution) for biomarkers related to CFI-402257: University Health Network. All other authors have declared no conflicts of interest.