Biotech Strategy Blog

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

Over the last decade we have seen some real progress with some subsets of lung cancer, particularly in EGFR mutated and ALK translocated tumours.  Indeed, an incredible amount of translational work has emanated from just a few groups based in Boston, New York and Hong Kong.

Dr Jeff Engelman Source: MGH

Dr Jeff Engelman Source: MGH

At AACR earlier this year, Dr Jeffrey Engelman (MGH, Boston) gave a fantastic talk not just about heterogeneity, resistance mechanisms, but also on how lung cancer can transform. Included in his review was the role of biospies and how he sees those evolving.

I’ve been meaning to write up this important talk since April, but decided to wait until the key publications that were in press at the time were actually published – it was a longer wait than expected!

In general, it is our policy to write up published, rather than unpublished data, out of respect to researchers.  It also makes it more useful to readers when the translational and clinical data is publicly available for those interested in reading the in-depth research articles.  We also gathered commentary from other though leaders in the lung cancer space for some additional insights.

To learn more about the latest developments in the underlying complexity and clinical implications for EGFR+, T790M-positive and ALK-positive lung cancers, subscribers can log in below or you can sign up to read our comprehensive review of this topic.

One of the interesting questions raised by the recently announced and much-discussed Juno/Celgene collaboration is whether you really need a Chimeric Antigen Receptor (CAR) T cell therapy in your portfolio to succeed as a global cancer immunotherapy company?

One leading cancer immunotherapy company that believes you don’t is Roche.  At ASCO 2015 I had the privilege to talk about this with a leading cancer scientist, William Pao, MD PhD (pictured below). Dr Pao formerly worked with Nobel Prize-winning scientist Harold Varmus at Memorial Sloan Kettering, and subsequently led the Hematology-Oncology Division at Vanderbilt. He joined Roche in July 2014 to lead their early development of innovative oncology new products (see press release).

Dr William Pao Roche

I particularly enjoyed Dr Pao’s discussion of the T-cell centric strategic framework around which the Roche/Genentech cancer immunotherapy portfolio strategy is based.

If you haven’t done so already, do listen to Episode 3 of the Novel Targets podcast (ASCO Lung Cancer Show) in which you can hear an excerpt from my interview with Dr Pao.

This is the first in a series of interviews with scientific leaders at companies at the forefront of cancer research.

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Yesterday, Juno Therapeutics and Celgene announced a ten year collaboration that is expected to close in July-August.  In short, Celgene has exclusive right to entire the Juno portfolio in oncology and auto-immune cell therapy products in development outside North America and co-promote certain programs globally (not specified).  Juno, meanwhile, gains the option to co-develop and co-promote select Celgene programs (also not specified).

You can see the terms of the deal here.

And listen to the webcast from the call after hours.

This news comes hot on the foot of an earlier announcement that the FDA accepted the Juno IND for JCAR017, a CD19 CAR T cell therapy being developed in relapsed/refractory NHL scheduled to initiate in 2015, with the possibility of a registration trial commencing in 2016.

What was fascinating, however, was the BioTwitter reactions last night – predictably, people either loved or hated the news – it clearly came as a surprise to many.

This morning my inbox is full of questions on this dramatic topic from subscribers, so here are some topline thoughts on this issue to answer the questions coming in.

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Immune checkpoint inhibitors that target CTLA4, PD1 and PDL1 can generate prolonged responses in a minority of patients, but the results so far in prostate cancer have been disappointing. Prostate cancer doctors have not been part of the excitement spreading through the cancer community like a “Mexican wave.”

Prostate cancer has not featured significantly in the cancer immunotherapy news recently, but that’s not to say there is not a lot going on. The phase 3 trial results of ipilimumab (a checkpoint inhibitor of CTLA-4) in the pre-chemotherapy setting of advanced prostate cancer (NCT01057810) are expected soon and there is also the eagerly awaited phase 3 trial of the PROSTVAC vaccine (NCT01322490).

Dr James Gulley ASCO 2015

At ASCO 2015, BSB interviewed Dr James L. Gulley, MD, PhD Chief of the Genitourinary Malignancies Branch and Director of the Medical Oncology Service at the National Cancer Institute (pictured above).

He talked about some of the cancer vaccine work he has done as part of the CRADA (Cooperative Research and Development Agreement) between the NCI and Bavarian Nordic, as well as strategies to help immunotherapy work in those tumors such as prostate cancer that are non-inflamed, where there may be an insufficient immune response for checkpoint inhibitors to work effectively.

Readers may recall we interviewed him at ASCO GU earlier year, “How to make non-immunogenic cancer sensitive to checkpoint inhibitors.” His outstanding work could shape the future of prostate cancer immunotherapy.

This post also includes additional ASCO 2015 commentary on from Dr Oliver Sartor, Professor of Cancer Research at Tulane University, who shared his perspective on the ipilimumab and PROSTVAC phase 3 prostate cancer trials that are due to readout soon.

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Many years ago, I used to work in the sarcoma and GIST space, which is a very interesting and fascinating disease to explore from a biology perspective. There are many different subsets of sarcoma, several different histologies, as well as numerous targets such as KIT in gastrointestinal stromal tumours (GIST). Some of these subsets are sensitive to chemotherapy such as doxorubicin, while others such as GIST are sensitive to targeted therapies including imatinib, sunitinib, regorafenib etc. Imatinib (Gleevec) is particularly effective in GISTs with exon 11, while the less common exon 9 has been shown to be more sensitive to sunitinib (Sutent), for example.

Often pharma companies will work with the Sarcoma Alliance for Research through Collaboration (SARC) cooperative group to undertake a phase 1 allcomers trial to evaluate which subsets might be appropriate for a given therapy, before exploring a narrower inclusion/exclusion criteria in a larger phase 2 or 3 study.  You can check out their current clinical trials in sarcomas here.

Overall, people with malignant sarcomas tend to be seen by specialist centres where there are usually clinical trials available, representing a way to determine which of the agents in development are superior to the current standard of care.

Dr Margaret von Mehren

Dr Margaret von Mehren

One of my favourite moments at ASCO this year was escaping the heavily mobbed poster halls to sit down for a quiet ‘fireside chat’ and catching up with an expert in this field to learn more about the latest new developments in sarcoma.

I’m delighted to publish another thought leader discussion today on Biotech Strategy Blog (BSB), where we have an in-depth interview with Dr Margaret von Mehren, the Director of Sarcoma Oncology at Fox Chase Cancer Center.  She has spent spent her career trying to identify new therapeutics for gastrointestinal stromal tumours (GIST), as well as soft tissue sarcomas (STS).

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In today’s post, it’s time to address a bunch of questions we’ve received over the last few weeks from subscribers about the latest and – not so greatest – in cancer research.

Chicago City View

ASCO 2015 Chicago

Sometimes these queries are fairly straightforward to answer, other times requires some sleuthing and hunting down thought leaders for some additional context and insights… For obvious reasons, these folks are best caught in person at cancer conferences such as AACR and ASCO.  The feedback isn’t always sparkly and positive though, it can also be gloom and doom, just like the inclement weather!

So here goes, questions on the following are covered in the article below:

  • Neratinib
  • Bavituximab
  • Gilead
  • Enzalutamide
  • MDSCs

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Anyone who has been regularly to the American Society of Clinical Oncology (ASCO) over the last decade or two will have have sat through quite a lot of trials with doublets and triplets in numerous advanced solid tumours and seen an impressive graveyard of failed cytotoxics and targeted therapies build up… Too toxic, lack of efficacy, futile even. This is especially true for some of the more difficult to treat cancers such as pancreatic, small cell lung cancer, melanoma, glioblastoma and soft tissue sarcomas.

Chicago Riverwalk

ASCO 2015

There is hope though, after all, things have changed quite dramatically in the metastatic melanoma landscape over the last five years that it is now quite unrecognisable compared to a decade or even five years ago. This is very good news indeed.

What about the other tumour types in that list, though? How are we making progress with those?

In the latest series here on BSB, we’re going to focus on the new developments happening on the fringes of cancer research out of the main spotlight and look in more depth at what’s looking promising in some of these areas. Today, we’re going to start with small cell lung cancer (SCLC), a truly devastating disease with a horribly dismal prognosis.

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We’ve heard a lot about agents that target the PD–1/PD-L1 pathway over the last two years, in particular, from:

  • Nivolumab (BMS)
  • Pembrolizumab (Merck)
  • Atezolizumab (Roche/Genentech)
  • MEDI–4736 (AstraZeneca/MedImmune)

What about other agents against this pathway that are in earlier development? It really doesn’t take long for a new space to become quickly crowded and very competitive, as the Pharma R&D machines start cranking out results from clinical trials.

A critical question that will to be considered is how will the third, fourth or even 19th agent to market differentiate themselves from those already approved and established? Is it realistic to expect a blue ocean strategy approach or will the pieces of the pie become ever smaller?

At the annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month, there was new data presented from other companies on checkpoint inhibition.  We took at look at some of the emerging data in more detail.

To learn more about the increasingly competitive anti-PD1/PDL1 pathway market, check out our insights in the mini report below.

One interesting aspect of the recent American Society of Clinical Oncology (ASCO) meeting was the surprise many people expressed in conversations that chemotherapy might actually be useful in combination with checkpoint inhibitors.

You see, several years ago when we first started writing about this new class of agents, I remember vividly how quite a few analysts grumbled on social media or sent me snarky personal messages when it was even suggested that this — along with combinations with existing targeted therapies — might be a worthwhile and valid approach to explore. Clearly they believed that immunotherapies (as monotherapy) were going to be the ultimate panacea.

Not so fast…

There are a number of scientific reasons for combination strategies, but not everyone thinks rationally when new approches come along and their attititude is often ‘out with the old, in with the new!’ It was actually quite amusing to see some of the very same folks in Chicago now eulogising the combination of checkpoint blockade with… chemotherapy in lung, colorectal or even bladder cancer.

One reason why these traditional therapies may be important is because they can influence the tumour microenvironment in both positive and negative ways. That can be helpful for deciding on rational future combinations, rather than just throwing mud at the wall and hoping based on a limited set of data.

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