1. Brian Boulmay, MD LSUHSC- New Orleans Section of Hematology & Oncology
ASCO Rehash 2016
Brian Boulmay, MD
LSUHSC- New Orleans
Section of Hematology & Oncology
*many slides adapted from ASCO2016 vitual meeting

2. Pembrolizumab Plus Chemotherapy as Front-Line Therapy for Advanced NSCLC: KEYNOTE-021 Cohorts A-C
Abstract 9016
Gadgeel S, Stevenson J, Langer C, et al.

3. Background
Standard of care for mNSCLC without mutation is stil a platinum doublet.
Pembrolizumab has efficacy for previosuly treated NSCLC
The KEYNOTE- 10 trial established an improvement in overall survival when compared to docetaxel.
12.7 months v 10.4 months
For tumors with >=50% PDL1 expression:
14.9 v 8.2 months
Pembrolizumab is approved for use in the US in the second line after a platinum-based doublet in tumors that express PDL1
Herbst The Lancet 2016

4. Phase I/II trial of pembro + platinum based doublet first line.
Study Design
Phase I/II trial of pembro + platinum based doublet first line.
Key Eligibility:
Age 18-75, any NSCLC histology, EGFR and ALK wild-type, no active CNS mets….and any PDL1 status.

5. Study Schema

6. Results: Baseline Characteristics

7. Results: Baseline Characteristics

8. Three patients in cohort B stopped study drug due to AEs
Safety Signals
Three patients in cohort B stopped study drug due to AEs
Grade III pneumonitis
Grade III drug hypersensitivity
Grade III colitis
No treatment related deaths

9. Immune-Related AEs

10. RESULTS: ORR

11. RESULTS: ORR

12. PFS
Median 10.2 months
Median: 10.3 months
Median: NR

13. Overall Survival
Median: NR
Median: NR
Median: NR

14. Chemotherapy plus pembrolizumab appears to be well tolerated
Conclusions
Chemotherapy plus pembrolizumab appears to be well tolerated
Exception is bevacizumab containing regimen
Keynote 189- evaluating pem/platinum +/- pembrolizumab is recruiting for Non-SqNSCLC
Keynote 407- evaluting Taxol/platinum +/- pembrolizumb is recruiting for SqCCa

15. Antonia S, et. al. Abstract 100
Checkmate 032: Nivolumab Alone or in Combination with Ipilimumab for the Treatment of Recurrent Small Cell Lung Cancer
Antonia S, et. al. Abstract 100

16. Small cell lung cancer Trivial progress in the last three decades
Good responses, recurrence is the rule
Second line therapy basically ineffective

17. Small cell lung cancer
Small cell lung cancer is generally felt to be a ‘cold tumor’
T-cell infiltrates are sparse
Unlike melanoma, NSCLC
In theory, immune therapy with PD1 would not be effective.
No T-cells to activate

18. Ipilimumab is not active in the tumor environment, but in the lymphoid compartment
May enhance T-cell infiltrate of cold tumors

19. Checkmate 032

20. Checkmate 032

21. Checkmate 032
Tocixity:
79% had toxicity of any grade in the Nivo1+Ipi3 arm.
Diarrhea and fatigue most common
4% pneumonitis

22. Checkmate 032

23. Checkmate 032

24. Checkmate 032

25. Conclusions Safety profile is similar to other diseases.
Durable objective response rates
Tumors responded despite low PDL1 expression
Nivo1/Ipi3 chosen for further study
Checkmate 032 expanded
Checkmate 451 maintenance

26. Plug AZ Trial to open at LSU
Durvalumab plus tremelimumab first line NSCLC