Page 24 - PD-L1 EbookV2 Flip PDF

The PD-L1 case: Immune checkpoint inhibitors and the lack of robust
biomarkers

Many experts say that out of all the therapies developed to harness the power of the
immune system to fight cancer over the past several decades, PD-1/PD-L1 inhibitors
look to be the most promising, even though it is still relatively early days in their
development. Maria Fe Paz and Patrick Considine of Diaceutics suggest that there is
an urgent need to standardize and harmonize the assays used to evaluate PD-L1
expression, and for integrative initiatives to support the ongoing collaborations
amongst the many different key stakeholders.
T
here is no doubt that immuno-oncology is a paradigm shift holding much promise in
cancer treatment. The idea of boosting the immune system to fight against its own
malignant cancer cells has provided a strong rationale and focus to researchers for
decades, working to translate their studies from the bench to the clinic. Understanding the
checkpoints responsible for the immunomodulation was key to facilitating the identification of
drug targets, and development of monoclonal antibodies that are showing promising results
in the clinical setting.

Not only the medical community, but many other stakeholders, are following with excitement
the development of these immune checkpoint inhibitors. Some of the major pharmaceutical
companies have initiated clinical trials, using immune checkpoint inhibitors as single
therapies or in combination with other therapies for a range of cancers and an increasing
scope of indications. The relatively mild safety profile makes them ideal for combinations,
and they will very likely become the backbone of most cancer treatment schemes in the next
years. Many experts say that out of all of the therapies developed to harness the power of
the immune system to fight cancer over the past several decades, PD-1/PD-L1 inhibitors
look to be the most promising, even though it is still relatively early days in their
development.

Biomarkers of response

In this competitive landscape, in which the market share will be at least partially influenced
by the first comers to market, there is a growing need to improve the clinical outcomes to
grant faster approvals. A recent Goldman Sachs review suggests some companies with
1
PD-1/PD-L1 inhibitors are betting initially on an ‘all-comers’ strategy, i.e., no requirement to
segment patients based on biomarker profile. Such a strategy appears to fit those first into
the market with a specific indication such as melanoma and other second line or smaller
third indications. BMS have embraced this strategy for Yervoy in melanoma indication and
for Opdivo in melanoma indication and third line squamous NSCLC. Merck has adopted the
same strategy for Keytruda in melanoma indication and first NSCLC indication. Whilst the
early clinical studies may support the ‘no biomarker’ strategy, the move of PD-1/PD-L1
therapies into first line may require the incorporation of a biomarker strategy.

The complexity of the interaction between the immune system and the tumor cells, the role
of the microenvironment and other factors yet to be determined, are challenging the
application and validation of the one single biomarker of response. Given the scenario in

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