Biotech Strategy Blog

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

Posts tagged ‘AACR 2015 Checkpoint Inhibitors’

After yesterdays post on Gems from the Poster Halls at the American Association for Cancer Research (AACR) in Philadelphia where we took a look at new developments in targeted therapies, several subscribers asked for a repeat, but with a focus on immuno-oncology.

AACR 2015 Checkpoint Inhibitor PostersThere are a number of elements that many people are interested in, especially given the Merck and BMS clinical data at AACR, where we clearly saw that:

  • Anti-PD–1 therapy with pembrolizumab is superior to anti-CTLA4 with ipilimumab in metastatic melanoma (expect nivolumab to show the same thing at ASCO)
  • Combined PD–1 plus CTLA4 blockade (with nivolumab plus ipilimumab) was superior to anti-CTLA4 alone, but with higher grade 3/4 toxicities, also in advanced melanoma

Sadly though, we still see that 70-80% of patients don’t respond to these therapies.

  • How can we improve on that?
  • What happens when we explore other factors, tumour types and different aspects of the immune system?
  • What can we learn about novel sequencing or combination approaches?
  • Which ones look interesting?

Endless questions can be asked – to which we still have too few answers – although there were some encouraging signs and hints of possibilities at AACR.

The 2015 AACR program was particularly challenging this year with lots of really good symposia and general sessions, making it tough to whizz round the vast poster hall spread out around the exhibits as well.  To give you an idea of scale, it was pretty typical to cover 17K to 18K steps a day, approximately 7 to 8 miles.  For many people, fitting in a quick lunch and the posters was certainly a challenging feat, depending where you were in the complex.  With a morning session ending at 12.30pm, the afternoon session starting at 1pm and 2,000 steps between the Grand and Terrace Ballrooms, you sure had to get your skates on, Beep Beep!

To learn more about the latest data in these areas, especially from the small up and coming biotechs, you can sign up or sign in below.

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One of the obvious learnings from the American Association of Clinical Research (AACR) meeting earlier this week was that we are coming to the end of the low hanging fruit opportunities for checkpoint inhibitors as monotherapies.

Speaking with numerous company people in this space, there was wide consensus on that point. As one clinical lead put it succinctly, “From here on out, it’s going to get way more complicated – had a low grade headache develop after the very first science session I attended – and it’s still there after two days!”

How many of us know that feeling all too well?  AACR always has the heaviest science load of any cancer conference we attend each year. Sure there’s some nice clinical data, but that is like nibbling on the light appetizers before the 20 course banquet. You need much stamina and fortitude to survive the brain fog at AACR. Then there’s the glee at snagging some key poster handouts at the meeting, only to be rapidly diminished when you try to read the 4pt print post hoc and realise your eyes cannot focus easily.

Looking at the long list of topics I want to cover in the in-depth post meeting analysis for a ‘lighter’ post, especially given that it’s Friday after a very long week, that sinking feeling hit home hard – there are no lightweight topics at AACR.

The other day, we posted about the promising data in triple negative breast cancer (TNBC), following on from the Genentech and Merck presentations at the San Antonio Breast Cancer Symposium (SABCS). These data surprised many folks, mostly because they didn’t consider breast cancer to be an immunogenic tumour – nor is lung cancer in the broader scheme of things for that matter – yet we are seeing some nice durable responses in both tumour types with checkpoint inhibitors.

In other words, our definition and perceptions must change as we redefine how we identify and think of possible ‘responsive’ cancers to these agents.

So where are likely heading next?

To learn more about future directions with checkpoint inhibitors, you can sign in or sign up below.

Quick Reminder: Today is the last day for the AACR Special – the discount ends at midnight ET tonight. We may not offer this rate again as it’s a limited time only deal!

Philadelphia – it’s the final day of the American Association of Cancer Research (AACR) annual meeting, and it’s been one of the best AACR annual meetings of recent years, with cancer immunotherapy very much at the fore.

This morning, the plenary session at the meeting was: Oncology Meets Immunology: Not Just Another “Hallmark.”

Cancer immunotherapy is changing the paradigm of cancer treatment in many ways, which is why the title of today’s plenary was clever….

Readers will be aware of the classic Hallmarks of Cancer paper (open access) by Douglas Hanahan and Robert Weinberg, which provides a framework for understanding how how tumors develop (e.g. sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis). This landmark paper provides a way to understand where new cancer treatments could act.

Today’s plenary featured four presentations from leaders in the field of cancer immunotherapy:

  • Engineering Improved Cancer Vaccines, Glen Dranoff, Novartis Institutes for Biomedical Research
  • Leukocytes as targets for therapy in solid tumors, Lisa M. Coussens, OHSU Knight Cancer Institute, Portland
  • Fatal Attraction: A new story featuring the immune system and pancreatic cancer, Elizabeth M. Jaffee, Johns Hopkins University, Baltimore
  • The mechanistic basis of cancer immunotherapy, Ira Mellman, Genentech, Inc. South San Francisco.

The first three speakers I have to say did not live up to the promise of their billing, spending far too much time on “My Pet Project,” delving into the weeds of the research from their lab or group, rather than putting the landscape in context, providing strategic direction of where things are going and including fair balance across the work in the field, which is what I expected a plenary presentation to be about.

One of our highlights of the plenary (and the conference) was the presentation by Ira Mellman, Vice President at Genentech who along with Dan Chen, Cancer Immunotherapy Franchsise Head at Genentech, are the author of the paper that is fast becoming the equivalent of the classic Hallmarks paper for Cancer Immunotherapy: Oncology meets immunology: the cancer-immunity cycle. (open access).

Dr Ira Mellman Dr Leisha Emens Dr Dan Chen AACR 2015

Earlier in the meeting, I had the privilege to chat with Drs Ira Mellman (pictured left), Leisha Emens (Johns Hopkins) and Dan Chen (pictured right) for the Novel Targets podcast. They are three of the many “rock stars” of the cancer immunotherapy world.

What were our highlights of AACR 2015?

We’ve carefully selected our Top Ten presentations of this year’s AACR for subscribers – Ira Mellman’s was one of them – but who are the others?  Some of them could be found outside the main sessions in the fringe rooms.

You can login in below or can purchase access to read them in the box.

For the week of the AACR meeting, there’s $50 off the price of a quarterly subscription, that will get you not only our post-AACR conference coverage, but access to the library of content we’ve written for example on immuno-oncology.

We’ll be at four meetings, including ASCO in the next two months, so to paraphrase Frank Sinatra, “The best is yet to come”…….

Recently, Merck have been on a roll in the immuno-oncology space, with the announcement that their anti-PD–1 antibody, pembrolizumab (Keytruda), beat out BMS’s anti-CTLA4 antibody, ipilimumab (Yervoy) in a Phase 3 head-to-head frontline trial in metastatic melanoma. The two primary endpoints of OS and PFS were met and the trial will therefore be stopped early based on the IDMC recommendation. No further details are available until the presentation.

merck_logoThe data from the KEYNOTE–006 study is being presented at the annual American Association for Cancer Research (AACR) next month in the opening plenary session by Dr Antoni Ribas (UCLA).

While it’s nice to see evidence that one checkpoint inhibitor is potentially superior to another, in the long run, combinations are likely to be the best way forward.  This approach is more likely to yield improved responses in immunogenic tumours, but also to make non-immunogenic tumours more responsive, thereby improving patient outcomes further.

This begs the all important question – what hints from new emerging data can we glean that will help us figure out novel combination approaches with checkpoint inhibitors?

To learn more about this, you can login in or sign up in the box below.

Today I’m answering recent questions from readers, in this case on checkpoint inhibition and where this field is going in the near future.

No doubt we can expect to hear a lot of new data and research being presented at the upcoming AACR and ASCO conferences, so this is a timely point to reflect on a few topics of relevance.

To learn more super cool and groovy immuno-oncology stuff, you can sign up or log-in in the box below.

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