1. KEYNOTE-021: Pembrolizumab + Ipilimumab Active in Previously Treated Advanced NSCLC CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*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 program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. KEYNOTE-021 NSCLC Cohort: Background
Pembrolizumab: humanized IgG4 antibody to PD-1 immune checkpoint[1]
Blocks PD-1 binding to PD-L1 and PD-L2
Single-agent activity in pts with advanced NSCLC[2]
Ipilimumab: fully human IgG1 antibody to CTLA-4 immune checkpoint[3]
In advanced melanoma and NSCLC, combined anti–CTLA-4 and anti– PD-1 treatment has shown robust efficacy along with manageable toxicity[3-5]
KEYNOTE-021: phase I evaluation of Ipi + Pembro in previously treated pts with advanced NSCLC[1]
Ipi, ipilimumab; NSCLC, non-small-cell lung cancer; Pembro, pembrolizumab.
1. Patnaik A, et al. ASCO Abstract Garon EB, et al. N Engl J Med. 2015;372: Wolchok JD, et al. N Engl J Med. 2013;369: Postow MA, et al. N Engl J Med. 2015;372: Antonia SJ, et al. J Clin Oncol. 2014;32. Abstract 8023.

3. KEYNOTE-021 Advanced NSCLC Cohort: Ipilimumab + Pembrolizumab
Standard dose escalation[1]
Ipi (0.3, 1, or 3 mg/kg) + Pembro (2 or 10 mg/kg) q3w
Protocol amended during study to treat all subsequent pts with Ipi 1 mg/kg + Pembro 2 mg/kg q3w based on toxicity concern[2]
Primary endpoint: DLTs in first 3 weeks
Secondary endpoints: safety and tolerability, ORR
Ipilimumab 4 doses
Previously treated advanced/metastatic NSCLC including ≥ 1 platinum doublet CT, ECOG PS 0/1 Wk
/// 105
CT, computed tomography; DLT, dose-limiting toxicities; ECOG PS, Eastern Cooperative Oncology Group performance status; Ipi, ipilimumab; NSCLC, non-small-cell lung cancer; ORR, overall response rate; Pembro, pembrolizumab; q3w, every 3 weeks.
Pembrolizumab up to 2 yrs
1. Patnaik A, et al. ASCO Abstract Reprinted with permission. 2. Antonia SJ, et al. ASCO Abstract 8023.

4. KEYNOTE-021 NSCLC Cohort: Ipi + Pembro Adverse Events
AEs Observed in ≥ 3 Pts, n
Ipi 3 mg/kg + Pembro
10 mg/kg
(n = 3)
Ipi 1 mg/kg + Pembro 10 mg/kg
Ipi 1 mg/kg + Pembro 2 mg/kg
(n = 12)
Total
(N = 18)
Any 3 9 15
Fatigue 1 2 4 7
Decreased appetite
Myalgia
Pruritus
Rash
AEs, adverse events; DLT, dose-limiting toxicities; Ipi, ipilimumab; NSCLC, non-small-cell lung cancer; Pembro, pembrolizumab.
No pts experienced DLTs
3 grade 3 events: adrenal insufficiency, drug eruption, maculopapular rash
No treatment-related grade 4/5 events
2 pts discontinued treatment due to AEs
Patnaik A, et al. ASCO Abstract 8011.

5. KEYNOTE-021 NSCLC Cohort: Tumor Response
100 80 60
71% of patients showed decrease in target lesion burden 40 20
Change From Baseline, %
-20
-40
-60
-80
-100
-120
CR, complete response; NSCLC, non-small-cell lung cancer; ORR, overall response rate.
Pembrolizumab 10mg/kg + ipilimumab 1 or 3 mg/kg
Pembrolizumab 2mg/kg + ipilimumab 1mg/kg
ORR (N = 18): 39% including 1 CR
Patnaik A, et al. ASCO Abstract Reprinted with permission.

6. KEYNOTE-021 NSCLC Cohort: Treatment Exposure and Response Duration
All responses ongoing at the time of data cutoff
Response duration: 6+ to 39+ wks
CR as best response PR as best response
PD as best response Last pembrolizumab dose Treatment ongoing
Pembrolizumab 10mg/kg + ipilimumab 1 or 3 mg/kg
Pembrolizumab 2mg/kg + ipilimumab 1mg/kg
CR, complete response; NSCLC, non-small-cell lung cancer; PD, progressive disease; PR, partial response. 6 12 18 24 30 36 42 48
Wks
The length of the bars is equivalent to the time to the last disease assessment by the investigator. Analysis cutoff date: March 31, 2015.
Patnaik A, et al. ASCO Abstract Reprinted with permission.

7. KEYNOTE-021 NSCLC Cohort: Conclusions
Toxicity profile of ipilimumab + pembrolizumab is manageable
No DLTs
17% rate of grade 3 AEs; no grade 4 or 5 AEs
Preliminary results suggest robust, durable antitumor activity with ipilimumab + pembrolizumab
Unselected, previously treated pt population
All responses ongoing at time of data cutoff
Evaluation of ipilimumab + pembrolizumab in advanced NSCLC ongoing
AEs, adverse events; DLTs, dose-limiting toxicities; NSCLC, non-small-cell lung cancer; ORR, objective response rate.
Patnaik A, et al. ASCO Abstract 8011.

8. Go Online for More CCO Coverage of ASCO 2015!
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