Biotech Strategy Blog

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

With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below.  Read on…

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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!

With the news hot off the press at the 2015 annual meeting of the American Association for Cancer Research (AACR) that Merck’s pembrolizumab (Keytruda) beat out BMS’s ipilimumab (Yervoy) in advanced melanoma, quite a few readers wrote in asking whether this signals the end for ipilimumab?

The short answer is no, and here’s why…

To find out why, you can sign in or subscribe to our Conference Coverage service in the box below.

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”…….

Philadelphia – at the 2015 annual meeting of the American Association for Cancer Research (AACR), new data was presented that showed checkpoint inhibitors have a greater effect when they work in combination, they may also offer a new effective treatment option in Triple Negative Breast Cancer (TNBC).

Are two checkpoints are better than one?

At AACR 2015, F. Stephen Hodi MD (Dana-Farber Cancer Institute) presented results, published simultaneously in the New England Journal of Medicine, that showed in advanced melanoma, combining two checkpoint inhibitors (nivolumab and ipilimumab) showed better results than with one alone (ipilumumab). The authors in their NEJM paper conclude:

The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. Combination therapy had an acceptable safety profile.

What is the potential for checkpoint inhibition in TNBC?

Yesterday at AACR, Leisha S. Emens MD, PhD (Johns Hopkins) presented the results in TNBC from a phase 1 trial of MPDL3280A (Roche/Genentech), a checkpoint inhibitor that targets the PD-L1/PD-1 signaling pathway.

Dr Emens (right) is shown in the picture below presenting at an AACR media briefing moderated by Louis M. Weiner MD, Dr Hodi is pictured left.

AACR 2015 Press Briefing

The only currently available treatment for TNBC is chemotherapy, but sadly patients often do not live long, and rapidly progress. Progression-free survival (PFS) is estimated to be around 4 months in TNBC. This means there is a real unmet medical need for effective new treatments. The fact that cancer immunotherapy, and in particularly checkpoint inhibitors targeting the PD-L1/PD-1 signaling pathway may have potential in this disease is huge.

Cancer immunotherapy and in particular checkpoint inhibitors are a hot topic at AACR. In this post we look in more detail at the data presented.

Subscribers can login to read more or you can purchase access below. This week in recognition of AACR, we are offering a $50 discount on the price of a quarterly subscription.

Philadelphia – the 2015 annual meeting of the American Association for Cancer Research (AACR) is in full swing, with over 18,000 attendees, it’s probably the world’s largest meeting dedicated to cancer research. The theme is “Bringing Cancer Discoveries to Patients.”

AACR 2015 Annual Meeting Philadelphia

I challenge anyone not to attend, and come away inspired with new ideas on how the field of cancer research will evolve in coming years.

At this year’s annual meeting, not surprisingly, cancer immunotherapy is one of the hot topics. Yesterday there was the simultaneous publication of two papers in the New England Journal of Medicine (NEJM) to coincide with data presented at the meeting.

Pembrolizumab (Keytruda)  for the Treatment of Non–Small-Cell Lung Cancer

The conclusion of the paper by Edward B. Garon, MD (UCLA) et al was that:

Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non–small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

The other paper published in the NEJM was for:

Pembrolizumab (Keytruda) versus Ipilimumab (Opdivo) in advanced Melanoma.

The conclusion of the paper by Caroline Robert, MD PhD, presented at AACR by Antoni Ribas, M.D., Ph.D.(UCLA) was:

The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.

AACR 2015 Press Briefing with Dr Topalian, Dr Ribas, Dr Garon

Dr Ribas (left) and Dr Garon (right) are pictured at an AACR media briefing chaired by Dr Suzanne Topalian (Johns Hopkins).

This year’s AACR annual meeting is to paraphrase Bertrand Tombal, “a Grand Cru year”. Not only in cancer immunotherapy, but in metabolism, epigenetics and advances in drug discovery.

We’re excited about the prospect of another three days at the meeting, but in the meantime in this post there’s some top-line thoughts for subscribers on some of the data that caught our attention over the weekend.

In recognition of AACR, there’s $50 off a quarterly subscription if you wish to purchase access (offer valid only during the week of the meeting – ends this Friday!)  If you’ve been sitting on the fence for a while wanting to try out BSB, now is a good opportunity to dip your toes in the water.

Subscribers can sign in below or you can purchase access by clicking on the blue icon at the end of the post.

European Lung Cancer Conference 2015Geneva – at the 2015 European Lung Cancer Conference today, Pasi A. Jänne, MD, PhD presented updated progression free survival and duration of response data for the phase 1 AURA trial of AZD9291 (AstraZeneca) in patients with EFGR-TKI-resistant advanced non-small cell cancer (Abstract LBA3).

Dr Jänne (pictured below at ASCO 2014) is Director, Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

Dr Pasi Jänne ASCO 2014

It’s hard to believe that it is only about two years since the first patient was enrolled in the phase 1 AURA trial of AZD9291, a third generation EGFR inhibitor. If the FDA regulatory submission takes place, as expected, in the second quarter of this year, then the drug could be approved for sale in the United States before the year end.

It has been fascinating to watch the race to market between rociletinib (Clovis Oncology) and AZD9291. It’s likely both could be approved in the United States before the year end.

That would be great news for lung cancer patients, given the absence of any approved therapy for patients who develop a T790M mutation and become resistant to EGFR inhibitors, such as Tarceva and Iressa.

Readers will know that we have been following the phase 1 AURA trial of AZD9291 since ECCO 2013 in Amsterdam, when the first clinical data was presented.

AstraZeneca are to be congratulated on what is a case study of rational scientific drug development; their path to market strategy highlights the benefit of well-designed early clinical trials. AZD9291 may end up receiving regulatory approval less than three years from the start of the first in man trial – that’s tremendous!

I had the privilege to interview Dr Jänne at ASCO last year, and again earlier this week, before he left Boston for Geneva and chatted with him about his AZD9291 presentation at European Lung.

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Much has been written about the success of checkpoint blockade in solid tumours over the last couple of years with the advent of anti-CTLA4 therapy (ipilimumab/Yervoy) for metastatic melanoma followed by the more recent approval of the anti-PD-1 antibodies in advanced melanoma (pembrolizumab/Keytruda and nivolumab/Opdivo) and lung cancer (nivolumab).

What about hematologic malignancies though?

At the recent American Society of Hematology (ASH) conference, we heard about the first clinical data for anti-PD1 antibodies in patients with refractory classic Hodgkins Lymphomas (cHL) and saw some impressive results. Interestingly, though, the early preclinical work was conducted in mice looking at CTLA4 blockade in a variety of tumours, both solid and liquid.

YervoyIs there a rationale for targeting CTLA4 in leukemias, lymphomas and even myeloma?  New data presented at a medical meeting in patients with heavily pre-treated and relapsed disease post stem cell transplantation suggests that this might be feasible.

Check out to today’s article to learn more about this clinical opportunity in more detail – you can log in or subscribe in the box below.

The 2015 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2015) was held in Istanbul last month, where it offered a European perspective on some of the latest developments in cancer immunotherapy. 

EBMT 2015 banner

We’ve heard a lot in the United States about the early CAR T cell therapy clinical trial results from institutions such as UPenn, CHOP, MSKCC, Fred Hutchinson, Seattle Children’s, the NCI, and MD Anderson to name but a few, so it was good to see a leading a European center join the club: University College London (UCL).

While completing a Masters degree in Human and Applied Physiology at King’s College London, I spent several weeks training at UCL and particularly enjoyed the intercollegiality of the University of London.

At EBMT15, Dr Sara Ghorashian Clinical Training Fellow at the Insitute of Child Health at UCL, presented data on a phase 1 trial of Epstein Barr virus (EBV) specific T cells transduced with a first generation CD19 Chimeric Antigen Receptor (CAR). The trial data was first reported by Dr Ghorashian (pictured below) in an oral presentation at #ASH14 (Abstract 383).

Dr Sara Ghorashian ASH 2014

Dr Ghorashian stated at EBMT that UCL have several CAR T cell therapy trials planned.

autolus-logoReaders will be aware that earlier this year that UCL spun-off a series A funded company, Autolus, to commercialize their CAR T cell therapy research.

Although £30m from Syncona (a subsidiary of the Wellcome Trust) is not a lot of money by US investment standards, UCL is nonetheless a European center to watch if you have an interest in the CAR-T competitive landscape.

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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?

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