FAK inhibitor targets cancer STEM cells

Dr. Weeks’ Comment: As more agents that target cancer STEM cells are patented (i.e made profitable) we will finally, as a society, stop targeting the benign cancer TUMOR cells and target the lethal cancer STEM cells.   Ask your oncologist to tell you how he or she will address your cancer STEM cells.  Your life depends upon it.



Phase 1/1b study of the FAK inhibitor defactinib (VS-6063) in combination with weekly paclitaxel for advanced ovarian cancer.

J Clin Oncol 32:5s, 2014 (suppl; abstr 5521)

Author(s):   Manish R. Patel, et al

Background: Defactinib (VS-6063) is an oral inhibitor of focal adhesion kinase (FAK). Blockade of FAK has been shown to reduce tumor growth and metastasis through inhibition of tumor cell survival, proliferation, invasion and tumor angiogenesis. FAK inhibitors also reduce the proportion of cancer stem cells (CSCs) while paclitaxel (PTX) treatment enriches for CSCs. This multicenter study investigated the safety/tolerability and activity of defactinib in combination with weekly PTX. Methods: Pts with advanced or refractory ovarian cancer were enrolled. In the Phase 1, defactinib was administered at either 200mg or 400mg BID with PTX 80 mg/m2 on days 1, 8, and 15, every 28 days. In the Phase 1b, an additional 12 pts were enrolled at a dose of 400 mg BID defactinib with 80 mg/m2 PTX. In pts with biopsiable disease, paired tumor biopsies were collected following a 10-day run-in with defactinib alone. Results:Eighteen pts were enrolled (6 in phase I and 12 in phase Ib): median age was 67.5 years (50-77); ECOG PS was 0 or 1. Pts received a median of 3 (1-9) prior regimens of therapy. All patients had prior taxane exposure and 15/18 (83%) were platinum resistant. The combination therapy was well tolerated with no DLT observed. The recommended dose was determined to be defactinib 400 mg BID with PTX 80 mg/m2. Reported treatment related grade 3 toxicities included: neutropenia (n=5), hyperbilirubinemia (3), thrombocytopenia (1), anemia (1), leukopenia (1), nausea (1), vomiting (1), increased alanine aminotransferase (1). No grade 4/5 drug related toxicities were observed. Defactinib did not alter PTX exposure. A decrease of p-FAK was observed in all 3 patients who underwent paired biopsies. One pt had a CR by RECIST, 1 pt has an ongoing PR of >6 months and 1 pt has ongoing SD of >8 months. Nine of the 18 pts remain on study. Conclusions: Defactinib was generally well tolerated in combination with weekly PTX, and further analysis of PD and biomarkers is ongoing. Radiographic tumor changes, normalization of serum markers, and tumor reductions in pFAK support further development of this combination. Clinical trial information: NCT01778803.

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