Table 2.

Summary of smoothened antagonist clinical trials with genetic analysis

Study by Author	Year	Cancer Type	Phase	Design	Treatment	Primary Endpoint	Target Inhibition	Ref #
Von Hoff, DDa	2009	Solid tumors	I	Open-label	Vismodegib	Safety	↓ GLI1 pt, correlates w/co	50
LoRusso, PMa	2011	Solid tumors	I	Open-label	Vismodegib	Safety	↓ GLI1 pt, correlates w/co	51
Rodon, J	2014	Solid tumors	I	Open-label	Sonidegib	Safety	↓ GLI1 pt, no correlation w/co	52
Jimeno, A	2013	Solid tumors	I	Open-label	Saridegib	Safety	↓ GLI1 pt, no correlation w/co	53
Bowles, DW	2016	SCC	I	Open-label	Saridegib + cetuximab	Safety	↓ HH pathway pt, correlates w/co	54
Wagner, AJ	2015	Solid tumors	I	Open-label	Glasdegib	Safety	↓ GLI1 pt, no correlation w/co	55
Goldman, J	2015	Solid tumors	I	Open-label	TAK-441	Safety	↓ GLI1 pt, no correlation w/co	56
Bendell, J.	2018	BCC	I	Open-label	Taladegib	Recommended Phase II	↓ GLI1 pt, no correlation w/co	46
Tang, JYb	2012	BCC	II	R, DB	Vismodegib	Reduced incidence of new BCC	↓ GLI1 pt, correlates w/co	57
Kaye, SB	2012	OC	II	Randomized	Vismodegib	PFS	No correlation	58
Berlin, J	2012	CRC	II	R, DB	Vismodegib + SOC	PFS	No correlation	59
Italiano, A	2013	CHS	II	Open-label	Vismodegib	Patients with non-PD at 6 months	No correlation	60
Kim, EJ	2014	PANC	II	Open-label	Vismodegib + SOC	PFS	↓ GLI1 pt, no correlation w/co	61
Robinson, GW	2015	MB	II	R, DB	Vismodegib	PFS	Correlation between baseline gene expression and co	62
Migden, MRb	2015	BCC	II	Open-label	Sonidegib	Objective response rate	↓ GLI1 pt, correlates w/co	63
Maughan	2016	PC	II	Open-label	Vismodegib	Pharmacodynamics	↓ GLI1 pt, no correlation w/co	64

^aBoth studies are based on the same clinical trial

^bServed as the basis for FDA approval

Abbreviations: BCC, basal cell carcinoma; CRC, colorectal cancer; CHS, chondrosacroma; OC, ovarian cancer; PANC, pancreatic cancer; PC, prostate cancer; SOC, standard of care; MB, medulloblastoma; SCC, squamous cell carcinoma; PD, progressive disease; R, DB, random, double blind; PFS, progression-free survival; pt, post-treatment; co, clinical outcome