Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘PD-1’

Insights from AACR on immunotherapy and checkpoint inhibitors

Today, I’m going to summarise some of my notes on what we learned about lung cancer and immunotherapy at AACR. The burgeoning immuno-oncology topic is way too big to do justice in one single post, so over the next couple of days, you’ll find a mini series evolving here on BSB to cover many of the points relating to checkpoint inhibitors from AACR. It was the first time in 15 years I’ve seen immunotherapy dominate a basic scientific meeting and it was good to see it happen. It is definitely very much the focus – and excitement – of many major cancer centres in the US.

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Novel targets and approaches in triple negative breast cancer

“You may say I’m a dreamer

But I’m not the only one.”

John Lennon, Imagine

As part of our ongoing series on the AACR Previews, today I want to take a closer look at some interesting scientific and clinical data in triple negative breast cancer (TNBC).  One reason for this is that we need to remember that the disease, as currently defined, is essentially what’s left after taking out the ER+, HER2+ and inflammatory breast cancer subsets. In other words, it’s a very heterogeneous catch-all population, making clinical trials rather challenging at best. It also means that the chances of success in general all-comer trials is rather low.

It is my hope that as we learn more about the biology of this disease, we may see further subsets be defined by molecular peculiarities, much in the same way that gastrointestinal stromal tumours (GIST) were defined by KIT expression and CD117. Once we have more homogenous subsets, it will be easier to conduct trials just looking at those specific patients, thereby improving the chances of clinical success with therapeutic intervention.

There’s been a lot of work focused on this area over the last few years, so it seems a good point to find out where the progress has got to.

Without much further ado, what can we learn about the biology of TNBC from AACR this year and which potential new targets might emerge?

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What to watch for at San Antonio Breast Cancer Symposium

Whew, having just finished the American Society of Hematology (ASH) meeting, we run on to the breast cancer symposium in San Antonio (SABCS), making for a very busy week of data deluge!  Our Post ASH analysis will also run concurrently for a few days.

There are also a number of interesting areas to look out for in terms of interesting breast cancer developments.

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Companies: Roche, GSK, AbbVie, AstraZeneca, Novartis, Lilly
Drugs: Herceptin, Avastin, Perjeta, Tykerb, veliparib, olaparib, BKM120, ramucirumab, PD-1, PD-L1

Here’s a quick preview of some of the landmark data emerging from this conference, some positive, some negative.

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A quick preview of the AACR Molecular Targets Conference

There are quite a few posters at the forthcoming AACR-NCI-EORTC Molecular Targets meeting this weekend that I wanted to highlight as potentially interesting and will additionally review in more depth once they have been published.

Please note: None of the embargoed abstracts are covered here in this preview to avoid any complications, but more detailed notes and reports will follow later on these from the conference as they are published.

Here some of the abstracts that caught my eye, in no particular order:

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A top line look at the PD-1 and PD-L1 abstracts at ECCO 2013

Amsterdam: Check point immunotherapy is probably on everyone’s hot topic list in oncology at the moment and rightly so.

ECCO Congress BannerOne of the key sessions I’m looking forward to at ECCO is the Saturday Lung Cancer Symposium on new therapeutic targets. It includes not only a presentation on PD-1 and PD-L1 Immune checkpoint antibodies, but also overviews of progress in several other pathways, namely PI3K-AKT-mTOR, RAS-RAF-MEK and ALK+/Hsp inhibitors. This should be an excellent session that allows a broad overview of many of the key areas of research in the disease.

Aside from a late breaker on the two-year ipilimumab data in metastatic melanoma, the check point abstracts I managed to find in the #ECC2013 program appear to be all posters.  Here are my quick notes ahead of the presentations for Premium Content subscribers:

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How new approaches in targeted immunotherapy with anti-PD-1 and PD-L1 may change cancer research

Background

For many years, scientists have tried – and failed – to develop techniques to activate the body’s immune system against cancer. The majority of these immunotherapy approaches, especially vaccines, simply didn’t have enough potency, or were based on a weak target that had little impact on advanced disease. The rationale for vaccines in cancer prevention is much stronger, as we have seen with the HPV vaccines, Gardasil and Cervarix, for example. When given to patients with advanced disease, the large tumour burden is usually too much for them to overcome and the cancer wins.

Although the immunotherapy field in oncology has been largely a graveyard with millions of dollars wasted and lost, there have been some notable successes. US approvals include rituximab (and other similar CD20 targeted antibodies) in B-cell malignancies, the IMiDs (thalidomide, lenalidomide, pomalidomide) in multiple myeloma, and ipilimumab, a human cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody in metastatic melanoma.

There are several interesting challenges with immunotherapies that must be overcome before successful therapeutics can be developed.

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ASCO 2013 Preview Video

In her annual preview video of what’s hot at ASCO 2013, Sally Church (@Maverickny) discusses several therapeutic areas with new data at the meeting including:

  • Immunotherapy (PD-1, PD-L1, CTLA-4)
  • CLL (GA-101, idelalisib, IPI-145)
  • Breast Cancer (palbociclib, PF-05280014)
  • Lung Cancer (LDK-378, AP26113)
  • Pancreatic Cancer (Abraxane, TH-302)

This video was originally published on Pharma Strategy Blog and includes an edited mechanism of action (MOA) for PD-L1 (courtesy of Roche/Genentech). Several people have since remarked it’s the first time they fully understood what “upregulation” meant.

If you missed the video, it’s well worth watching again in the run up to ASCO 2014.

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