Phase II LURET Study: Vandetanib Monotherapy Active in RET-Rearranged Advanced NSCLC CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. NSCLC, non-small-cell lung cancer. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

Phase II LURET Study of Vandetanib in RET+ NSCLC: Background RET gene rearrangements observed in 1% to 2% of NSCLC Vandetanib: oral TKI Inhibits RET, EGFR, and VEGFR activity Tumor shrinkage with vandetanib in pts with RET- rearranged NSCLC documented in case reports[1,2] Multicenter, single-arm phase II study evaluated vandetanib efficacy and safety in pts with RET- rearranged advanced NSCLC who failed ≥ 1 prior line of chemotherapy[3] NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor. 1. Gautschi O, et al. J Thorac Oncol. 2013;8:e43-e44. 2. Falchook GS, et al. J Clin Oncol. 2016;34:e141-e144. 3. Seto T, et al. ASCO 2016. Abstract 9012. Slide credit: clinicaloptions.com

LURET: Study Design Pts treated with vandetanib 300 mg PO QD Eligibility criteria Advanced nonsquamous NSCLC Positive for RET fusion gene on RT-PCR and FISH ≥ 1 prior chemotherapy regimen 20 yrs of age or older ECOG PS 0-2 Primary endpoint: ORR (by IRR committee) Secondary endpoints: DoR, DCR (CR + PR + SD), PFS, OS, safety, response of prior anticancer therapy DCR, disease control rate; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; IRR, independent radiology review; NSCLC, non-small cell lung cancer; ORR, objective response rate; PS, performance status; SD, stable disease. Slide credit: clinicaloptions.com Seto T, et al. ASCO 2016. Abstract 9012.

LURET: Baseline Characteristics 1536 pts screened for RET fusions Feb 2013 to March 2015 34 pts (2%) RET- fusion positive 19 pts enrolled (ITT population) 2 pts subsequently found ineligible 17 pts comprise primary efficacy analysis population Baseline Characteristic Pts (N = 19) Median age, yrs (range) 59 (41-80) Female, % 74 ECOG PS 0/1/2, % 47/42/11 Never smoker, % 68 Adenocarcinoma histology, % 100 Stage IV disease, % 95 1/2/≥ 3 prior lines chemotherapy, % 37/21/42 Response to first-/second-/third-line therapy, %* 26/25/0 RET fusion partners, % KIF5B CCDC6 Unknown 53 31 16 ECOG, Eastern Cooperative Oncology Group; ITT, intent to treat; NSCLC, non-small cell lung cancer; PS, performance status. *n = 19/12/8. Slide credit: clinicaloptions.com Seto T, et al. ASCO 2016. Abstract 9012.

LURET: Efficacy of Vandetanib Primary analysis: ORR 53% (90% CI: 31% to 74%) for 17 eligible pts Best efficacy outcomes observed in pts with CCDC6-RET fusions Median DoR: 5.6 mos (range: 1.5-9.1 mos) 2 pts with ongoing response for > 1 yr Outcome Overall (N = 19) Type of RET Fusion KIF5B-RET (n = 10) CCDC6-RET (n = 6) Unknown (n = 3) ORR, % 47 20 83 67 DCR, % 90 100 Median PFS, mos 4.7 2.9 8.3 1-yr OS, % 42 33 CI, confidence interval; DCR, disease control rate; DoR, duration of response; NSCLC, non-small cell lung cancer; ORR, objective response rate. Slide credit: clinicaloptions.com Seto T, et al. ASCO 2016. Abstract 9012.

LURET: Treatment-Related AEs Treatment-Related AEs (≥ 20% Pts), % Any Grade Grade ≥ 3 Hypertension 84 58 Diarrhea 79 11 Rash acneiform 63 16 Dry skin 42 5 QTc prolongation Anorexia 32 Creatinine increased Vomiting 26 Paronychia Proteinuria AE, adverse event; NSCLC, non-small cell lung cancer. Only 1 grade 4 AE (QTc prolongation); no grade 5 AEs AEs resulted in discontinuation in 4 pts (21%), dose interruption in 16 pts (84%), and dose reduction in 10 pts (53%) Slide credit: clinicaloptions.com Seto T, et al. ASCO 2016. Abstract 9012.

LURET: Conclusions Phase II data demonstrate activity with vandetanib in RET- rearranged advanced NSCLC Tumors with CCDC6-RET fusion showed best response to treatment No new or unexpected safety signals Hypertension constituted most common grade ≥ 3 AE (58%) Investigators conclude that further evaluation of vandetanib in pts with RET-rearranged advanced NSCLC is warranted Will require nationwide screening programs to identify pts with rare driver mutations AE, adverse event; NSCLC, non-small cell lung cancer Slide credit: clinicaloptions.com Seto T, et al. ASCO 2016. Abstract 9012.

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