A	B	C
1	Main
2		Brand Name	Zactima, ZD6474
3		Generic Name	vandetanib
4		Indication	NSCLC
5		Mechanism	EGFr and VEGFr blocker. IC50s (uM): VEGFR-2: 0.04, VEGFR-3: 0.11, RET: 0.13, EGFR: 0.50, VEGFR-1: >1, c-KIT: >20. 475 Da MW
6		People	Alan Barge, Clinical VP of Oncology.
7		Clinical Trials
8			Phase I
9			Well tolerated <300mg. AE include rash, diarrhea, QTc.
10			Terminal half-life > 120 hours
11			In Japanese study, 4/9 patients had tumor responses in refractory NSCLC
12
13			006 Phase 2 in 2L - #7016 ASCO 2006
14			PFS of Zactima at 100mg/300mg vs placebo in 127 pts with NSCLC receiving docetaxel after 1L platinum failure.
15			18.7wks for 100mg, 17wks for 300mg vs 12wks for placebo. P=0.074 for 100mg, 0.416 for 300mg. % prolongation of PFS was 57% and 21% for 100mg/300mg.
16			All histology, prior platinum, PS0-1, Brian mets allowable, 42% women, 50% adenocarcinoma
17			Side effects included rash, diarrhea and QT prolongation (asymptomatic).
18
19			003 Phase 2 in 2L/3L - #7000 - ASCO 2006 (Natale)
20			Two-part (double-crossover on progression or toxicity) study
21			Zactima monotherapy (300mg, n=83) vs Iressa monotherapy (250mg, n=85) in 2L/3L patients (failed platinum) n=168.
22			Zactima median PFS 11.9wks (or 11.0?) vs 8.1wks for Iressa. P=0.035, HR = 0.69 (0.50 to 0.96)
23			8% RR vs 1% RR for Iressa
24			45% disease control vs 34%. In followup, 43% vs 24% disease control rate.
25			PS0-1, life expectancy >12 wks, brain mets allowed, all histologies included
26
27			Phase 2 1L: Zactima vs Carbo+Tax vs. Zactima+Carbo+Tax
28
29
30			Trial 32 - Phase III 2L NSCLC: Taxotere +- Zactima 100mg n>1200 - results in mid-2008
31
32
33			Study 57 - Phase III 2L/3L NSCLC: Zactima vs Tarceva n=1150
34			Enrolled first patient 9/29/2006
35			300mg dose vs 150mg for Tarceva.
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40			www.snapfish.com
41			UN: geoffrey.c.meacham@jpmorgan.com
42			PW: jpmorgan