1. 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.

2. 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-e Falchook GS, et al. J Clin Oncol. 2016;34:e141-e Seto T, et al. ASCO Abstract 9012.
Slide credit: clinicaloptions.com

3. 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 Abstract 9012.

4. LURET: Baseline Characteristics
1536 pts screened for RET fusions Feb 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 Abstract 9012.

5. 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: 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 Abstract 9012.

6. 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 Abstract 9012.

7. 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 Abstract 9012.

8. Go Online for More CCO Coverage of ASCO 2016!
Short slideset summaries of all the key data
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Breast, Genitourinary, and Lung cancers
Hematologic malignancies
Immunotherapy
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