We have heard a lot recently about the monoclonal antibody Ipilimumab (anti-CTLA-4), a.k.a Yervoy, a.k.a. MDX-010, which made big news when it was approved for melanoma. The results for the phase 2 trial in first-line NSCLC were published in the June 10, 2012 issue of he Journal of Clinical Oncology.
Ipilimumab in Combination With Paclitaxel and Carboplatin As First-Line Treatment in Stage IIIB/IV Non–Small-Cell Lung Cancer: Results From a Randomized, Double-Blind, Multicenter Phase II Study
Thomas J. Lynch, Igor Bondarenko, Alexander Luft, Piotr Serwatowski, Fabrice Barlesi, Raju Chacko,
Martin Sebastian, Joel Neal, Haolan Lu, Jean-Marie Cuillerot, and Martin Reck
This mAb could be considered as a competitor to Bavi, along with the anti-PD-1 mAb, although they all have totally different MOA.
Here are the trial results, and some text from the above paper. Note that the trial enrolled patients with both squamous and non-squamous histology. There were no complete responses in any arm.
N = 66 in control, N = 68 in Ipilimumab (phased)
CP + I (phased) | CP + P | P
ORR: 32% | 14%
PFS: 5.1 | 4.2 months | 0.02
MOS: 12.2 | 8.3 months | 0.23
INTRODUCTION
Platinum-based chemotherapy combinations are
the standard of first-line care for patients with
advanced non–small-cell lung cancer (NSCLC)
with a median overall survival (OS) that ranges
from 8 to 12 months.1,2 Recent additions to the
standard chemotherapy of biologics, such as bevacizumab
and cetuximab, have made only modest
differences in survival, which necessitated new
therapeutic paradigms.3-6 One anticancer target
of current interest is cytotoxic T-lymphocyte
antigen-4 (CTLA-4), which is a negative regulator
of T-cell activation.7-10
Ipilimumab, which is a fully human monoclonal antibody, specifically
blocks the binding of CTLA-4 to its ligands (CD80/CD86).
This blockade augments T-cell activation and proliferation, which
leads to tumor infiltration by T cells and tumor regression.
....
DISCUSSION
Histology is emerging as a factor in selecting agents for NSCLC
treatment, as suggested by the fact that bevacizumab and pemetrexed
are approved treatments for nonsquamous NSCLC but not for squamous
NSCLC.56,57 In this trial, phased ipilimumab appeared to show
improved efficacy for squamous histology, but there was no apparent
benefit for nonsquamous histology. Although caution is warranted in
interpreting these subset data from a small phase II study, it is notable
that tumor-infiltrating T cells are more abundant in squamous
NSCLC.48,51,58 Additional trials in conjunction with translational research
are needed to confirm our findings in patients with squamous
NSCLC.
....
Note the control arm had 23% squamous carcinoma, the phased Ipilimumab arm had 31%.
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