By Dr. Raez

1. New Agents in the Treatment of
Advanced NSCLC:
Luis E. Raez MD FACP FCCP
Chief of Hematology/Oncology &
Medical Director
Memorial Cancer Institute
Clinical Associate Professor of Medicine
Herbert Wertheim College of Medicine
Florida International University

2. Research Support: Syntha
Genentech/Roche
Pfizer
Biodesix
MSD
Merck Serono
Lilly Oncology
Boheringer Ingelheim
Novartis
Astra-Zeneca
Clovis
Speakers Bureau/Stocks: None

3. Ramucirumab
Necitumumab
Osimertinib
Nivolumab
Pembrolizumab
Alectinib

4. Ramucirumab

5. REVEL: Study Design

6. Progression-Free Survival<br />ITT Population, Investigator Assessment

7. Overall Survival<br />ITT Population

8. Necitumumab

9. SQUIRE (CP11-0806): Phase III Trial of Necitumumab (IMC-
11F8) plus Gemcitabine and Cisplatin in SqCC NSCLC:
Design
Gem + Cis + Necitumumab
Q3weeks (N=545)
Gem + Cis
Q3weeks (N=548)
NSCLC
Squamous cell
ECOG PS 0-2
N=1093
Necitumumab
to PD
1:1 randomization
max of 6 cycles
Patient selection was not based in EGFR expression
Tatcher N, J Clin Oncol 32:5s, 2014 (suppl; abstr 8008)

10. Median OS (m)
Gem-Cis +
Necitumumab
11,5
Gem-Cis 9,9
HR 0,84
IC 95% 0,74-0,96
p value 0,012
Tatcher N, J Clin Oncol 32:5s, 2014 (suppl; abstr 8008)
SQUIRE: Phase III Trial of Necitumumab plus
Gem/Cis
in SqCC NSCLC: OS

11. • SQUIRE is the largest phase III trial exploring the first line
treatment of squamous cell lung cancer
• The study reached its primary endpoint
(OS: 11.5 vs. 9.9m; p=0.012)
• However, minimal delta in PFS and no difference in ORR.
• The combination of Necitumumab, Gemcitabine and
Cisplatin had a manageable toxicity profile.
• New therapeutic alternative for squamous cell lung cancer.
Tatcher N, J Clin Oncol 32:5s, 2014 (suppl; abstr 8008)
SQUIRE: Phase III Trial of Necitumumab plus
Gem/Cis in SqCC NSCLC: Conclusions

12. Osimertinib
(AZD 9291)

13. Slide 7

14. Slide 12

15. Slide 10

16. Slide 11

17. All-causality Adverse Events
Presented By Suresh Ramalingam at 2015 ASCO Annual Meeting

18. Conclusions
Presented By Suresh Ramalingam at 2015 ASCO Annual Meeting

19. Nivolumab

20. Slide 13

21. CheckMate 017 (NCT01642004) - Study Design

22. Overall Survival

23. Summary

24. CheckMate 057 (NCT01673867) Study Design
Presented By Luis Paz-Ares at 2015 ASCO Annual Meeting

25. Overall Survival

26. Treatment-related Select AEs

27. Summary

28. Pembrolizumab

29. Slide 6

30. PDL1 status and Survival with pembrolizumab (anti-PD1) in NSCLC

31. Lung Cancer Immunotherapy
Still More Questions than Answers?
• Delayed response?
• PFS vs. OS ?
• Toxicity?
• CNS penetration?
• Biomarkers?

32. Clinical Factors for Response?

33. Response Assessment in NSCLC

34. Pneumonitis in NSCLC

35. Slide 11

36. Slide 28

37. Alectinib

38. •BID = twice daily; ORR = overall response rate; IRC = Independent Review Committee;
PFS = progression-free survival; ECOG PS = Eastern Cooperative Oncology Group performance status
NP28761 study design
Withdrawal/long-term
follow up
or treatment beyond
progression
ALK+ NSCLC
patients who
progressed on
crizotinib
treatment
Alectinib 600mg BID
(based on phase I dose-escalation
phase1)
• Key inclusion criteria
• ALK+ NSCLC (by FDA-approved FISH
test)
• Disease progression following
crizotinib
• ECOG PS ≤2
• 1-week minimum washout between
crizotinib and alectinib
• Untreated or treated CNS
metastases allowed, as long as
asymptomatic and neurologically
stable
PD
1. Gadgeel SM, et al. Lancet Oncol 2014
• Primary endpoint
• ORR by IRC according to RECIST v1.1
• Key secondary endpoints
• Disease control rate
• Duration of response
• Progression-free survival
• CNS ORR by IRC
• Safety
• Patient-reported outcomes

39. •CI = confidence interval; SLD = sum of longest diameters; Data cut-off = 27 April 2015; For duration of response data, 40% of
responders had an event; * 2 patients had missing data or were not evaluable
NP28761: objective response rate by IRC
Response-
evaluable
population
(n=67*)
Responders (ORR, %) 35 (52.2)
[95% CI] [39.7; 64.6]
Complete response, n (%) 0 (0.0)
Partial response, n (%) 35 (52.2)
Stable disease, n (%) 18 (26.9)
Progressive disease, n (%) 11 (16.4)
Disease control rate, n (%) 53 (79.1)
[95% CI] [67.4; 88.1]
Median duration of
response, months (95% CI) 13.5 (6.7; NE)
Waterfall plot for BOR (by IRC)
140
120
100
80
60
40
20
0
–20
–40
–60
–80
SLDmax.decreasefrombaseline(%)
Patients
PD (n=11) SD (n=18)PR (n=35)
NE (n=1) Missing (n=2)

40. •*Including measurable and non-measurable lesions
Data cut-off = 27 April 2015; 1 patient with prior radiation had missing data or was not evaluable
NP28761: CNS ORR by prior radiation
All patients with CNS metastases* (n=52)
Alectinib (600mg BID)
Prior radiation
(n=34)
No prior radiation
(n=18)
Responders (ORR %) 26.5 66.7
[95% CI] [12.9; 44.4] [41.0; 86.7]
Complete response, n (%) 3 (8.8) 10 (55.6)
Partial response, n (%) 6 (17.6) 2 (11.1)
Stable disease, n (%) 20 (58.8) 5 (27.8)
Progressive disease, n (%) 4 (11.8) 1 (5.6)

41. • Alectinib (600mg BID) demonstrated robust and durable clinical
efficacy in patients with ALK+ NSCLC disease who had progressed on
prior crizotinib
– ORR 52%, median DOR 13.5 months, median PFS 8.1 months
– a notable clinical benefit with alectinib was observed in patients
with CNS lesions at baseline
• Alectinib was well tolerated, with a low incidence of grade ≥3
toxicities and no GI events leading to treatment withdrawal or dose
reduction
• Improvements were seen in global health status based on PRO
assessments
• A global phase 3 head-to-head trial of first-line alectinib versus
crizotinib is ongoing
Conclusions