Download Ipilimumab

Combined Nivolumab and Ipilimumab
or Monotherapy in Untreated Melanoma
J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.J. Grob, C.L. Cowey, C.D. Lao,
D. Schadendorf, R. Dummer, M. Smylie, P. Rutkowski, P.F. Ferrucci, A. Hill,
J. Wagstaff, M.S. Carlino, J.B. Haanen, M. Maio, I. Marquez-Rodas
NEJM, july 2, 2015
2015-08-26
R3. 박은지/ Prof. 맹치훈
Introduction
 Considerable progress in the treatment of metastatic melanoma has been
made in the past 5 years, with the approval of immune checkpoint–
blocking antibodies and, in parallel, agents targeting aberrant signaling in
the 40 to 50% of melanomas with BRAF mutations
 Ipilimumab
Anti–cytotoxic T-lymphocyte– associated antigen 4 (CTLA-4) antibody
- Up-regulate antitumor immunity
- Improvement in overall survival
- Responses : 10% ~ 15% of patients
-
-
Introduction
 Nivolumab & pembrolizumab
 Two anti–programmed death 1 (PD-1) antibodies
 Approved by the FDA in 2014
 After progression during ipilimumab treatment
 In patients with BRAF-mutated melanoma after progression during
treatment with a BRAF inhibitor
- Objective responses : 30 ~ 40% of patients
-
Nivolumab + ipilimumab vs ipilimumab
- Objective response rates : 61% vs 11%
- Complete responses : 22% vs 0%
-
Introduction
 ☞ To confirm and extend these findings, we report one of the coprimary
end points (progressionfree survival) of a randomized, double-blind,
ulticenter, phase 3 trial that was conducted to evaluate the safety and
efficacy of nivolumab alone or nivolumab combined with ipilimumab in
comparison with ipilimumab alone in patients with previously untreated
metastatic melanoma
Methods (1)
Assessments
Tumor response :
RECIST at 12 weeks after randomization, then every 6 weeks for 49 weeks,
and then every 12 weeks until progression or treatment discontinuation,
whichever occurred later
Progression-free survival :
The time between the date of randomization and the date of documented
progression or death, whichever occurred first
Primary end point :
Progression-free survival and overall survival
Secondary end points :
Objective response rate
Tumor PD-L1 expression as a predictive biomarker for efficacy outcomes
Safety
Result (1)
2013.07~2014.03
Total 1293
In 137 centers
Result (2)
Median PFS
Nivolumab
Nivolumab
Ipilimumab
Ipilimumab
6.9 months
11.5
2.9
Result (2)
Median PFS
Nivolumab
Nivolumab
Ipilimumab
Ipilimumab
14 months
14
3.9
Result (2)
Median PFS
Nivolumab
Nivolumab
Ipilimumab
Ipilimumab
5.9 months
11.2
2.8
Result (3)
Result (4)
- 34.5 %
- 61.9 %
- 5.9 %
Result (4)
Conclusion
Among patients with previously untreated advanced melanoma, we
found longer progression-free survival and higher rates of objective
response with nivolumab alone and with the combination of
nivolumab and ipilimumab than with ipilimumab alone.
Thank you !
T cell Priming and Activation:
Control of T cell activation
 The method of “Ipilimumab”
Disinhibited
response
Activated
Inhibited
IV. Immunostat blockade:
Anti-PD-L1 and PD-1
 PD-L1 (on cancer cells)
- distal immune modulator
- expressed broadly in multiple tissues
including T&B cells, DCs, macrophage)
- expressed in 20-50% of human cancer
 PD-1 (on T cells)
- binds to PD-L1/PD-L2
N Engl J Med 2012; 366:2517-2519
Anti-PD-1
Anti-PD-L1
Ipilimumab
BMS-936558