Biotech Strategy Blog

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

Posts tagged ‘Abraxane’

Crowds of People at ASCO 2016

The ASCO Wall 2016

There has been much frustration on many fronts at the number of trials that do not see a relationship between PD-L1 expression and response. Some do, but many don’t. This has lead to quite a few investigators suggesting that the IHC assay may not be as useful as originally hoped, for predicting response to checkpoint blockade or selecting patients for therapy.

While we often do see a trend for more responders with higher levels of expression, the main issue is that PD-L1-negative patients can also see some responses, albeit at a lower rate.

There are many factors that can affect the measurement:

  • Fresh vs. archival tissue
  • Heterogeneity within the tumour
  • Tumour cells (TC) vs. immune cells (IC)
  • Different antibodies used for each assay
  • The dynamic nature of the tumour microenvironment – does timing of the biopsy matter?
  • Human error – a pathologist has to eyeball the IHC readouts and decide the level of staining intensity

And so on. These are just a few examples of the factors that can potentially affect the results, making it quite a challenging test to undertake. There is also time – does the level of expression vary temporally depending on which prior therapies are administered?

It would be easy to be disheartened by this, but fear not!

There were some impressive new data presented at ASCO that were not only intriguing, but also show us a way forward on how a multi-factorial approach could be used in different tumour types. By this I mean we might end up with different tests used in conjunction for several different cancers in order to a) predict responders and non-responders and b) better select patients for appropriate regimens or clinical trials.

It’s not going to be as easy as one size (or test) fits all.  Sometimes a more more sophisticated approach will be needed.  New data at ASCO gave us hints on what’s to come in this direction.

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For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

ASCO16 Chicago 1

En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

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The 2014 ASCO Gastrointestinal (GI) Cancer Symposium takes place in San Francisco from Jan 16-18 and is the second meeting in this year’s oncology conference calendar. GI cancers include oesophageal, gastric, colorectal and pancreatic cancers, as well as hepatocarcinoma or HCC (liver).

You can follow any tweets from ASCO GI using the hashtag #GI14.

This year, the topics that most caught my eye in the program were pancreatic and gastric cancers.

This post provides insights on the key studies that looked interesting to me at this event, based on the schedule available.  The abstracts will be available on January 14th and can be accessed here.

Companies mentioned: Celgene, Lilly, Roche/Genentech, Aduro Biotech
Drugs mentioned:  Abraxane, Gemzar, ramucirumab, Avastin, Herceptin, GVAX

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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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