Table 3.

FAK inhibitor trials in breast cancer

Compound	Substrate	FDA status	Metastatic breast cancer trials
			Trials	Outcomes	Toxicities	Ref
PF00562, 271 (PF-271)		No approval	Ph I: PF-00562271 in patients with advanced non-hematologic malignancies, study completed.	In 20 response-evaluable patients with colorectal carcinoma, 7 had SD, 2 over 24 weeks.	Nausea, vomiting, headache, fatigue, diarrhea, peripheral edema, dizziness, anorexia, hypotension, dysgeusia.	[179]
GSK2256098		No approval	Ph I: GSK2256098 in subjects with solid tumors (NCT01138033), ongoing.	Recruiting		[180]
			Ph I: GSK2256098 plus trametinib (MEK inhibitor) in subjects with advanced solid tumors (NCT01938443)	Recruiting		[180]
VS-6063 (defactinib)/formerly PF04554878 (PF-878)		Approved as orphan drug for mesothelioma	Ph II: VS-6063 neoadjuvant in patients with surgical resectable malignant pleural mesothelioma (NCT02004028)	Recruiting		[180]
			Ph II: VS-6063 in patients with KRAS mutant non-small cell lung cancer (NCT01951690)	Recruiting		[180]
			Ph I: n Japanese subjects with non-hematologic malignancies (NCT01943292)	Ongoing	Fatigue, headache, increased bilirubin and diarrhea.	[180]
			Ph I/Ib: Paclitaxel plus VS-6063 in subjects with advanced ovarian cancer (NCT01778803)	In 18 patients, 1 CR, lPRand 1SD.	Neutropenia (n=5), hyperbilirubinemia (3), thrombocytopenia (1), anemia (1), leukopenia (1), nausea (1), vomiting (1), increased alanine aminotransferase (1)	[181]
			Ph I: PF-04554878 in patients with advanced non-hematologic malignancies (NCT00787033)	SD in 12 (33 %) patients once the dose reached ≥100 mg BID	Nausea (33 %), vomiting (31 %), unconjugated hyperbilirubinemia (28 %), fatigue (25 %), headache (19 %), diarrhea (19 %), and anorexia(17 %)	[182]
Yll	Y397siteofFAK.	No approval	Preclinical investigation			[183]

BC breast cancer, HR hormone receptor, MBC metastatic breast cancer, PD progressive disease, SD stable disease, TNBC triple-negative breast cancer