Biotech Strategy Blog

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

At the 2015 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting Barcelona on Friday, Dr Stephen Hauser (UCSF) presented the data for octrelizumab, an anti-CD20 monoclonal antibody, on behalf of the investigators in the OPERA trial.  This study compared octrelizumab to a standard of care at the time the study started i.e. IFN β-1a (Rebif).

Roche previously announced that ocrelizumab is the first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis (MS):

  • Ocrelizumab showed superiority to interferon beta-1a (Rebif®) in two identical Phase III studies in people with relapsing multiple sclerosis (MS), the most common form of the disease.
  • Ocrelizumab is the first investigational medicine to show efficacy in people with primary progressive MS in a large Phase III study.

In addition, Dr Montalban presented the latest data for octrelizumab in primary progressive MS versus placebo (there are no approved therapies for this segment) on behalf of the ORATORIO investigators.

Here on BSB we have extensively covered other anti-CD20 monoclonal antibodies such as rituximab, ofatumumab and obinutuzumab in oncology indications specifically associated with hematologic malignancies, so what’s special about this same target and the results in MS with a different chemical entity?

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Sarcoma is something we call one disease but actually represents 50-70 different histologies, which poses challenges for drug development.  Not only do you have to identify what’s the unique target, but it’s hard to accrue patients into trials, when a major center may only see a few of each sub-type.

Soft tissue sarcoma is an area of unmet medical need, and one I have been interested in since launching Gleevec in GIST (way back when) when I was fortunate to get to know many of the leading sarcoma experts.

Dr George Demetri

George D. Demetri, MD. Photo Credit: DFCI

One of these is Dr George Demetri, who is Director, Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

At the recent European Cancer Congress in Vienna, I had the privilege to talk with Dr Demetri about some of the latest research in soft tissue sarcoma.

We spoke about cancer immunotherapy, new small molecules and monoclonal antibodies, and the potential of targeting the epigenetic machinery.

A lot of what Dr Demetri is doing is currently “under the radar” and while he didn’t give any secrets away, he did give some sense of where some breakthroughs may occur in the not too distant future.  He also talked about how sarcomas with a specific target can be used for proof of concept clinical trials of novel agents.

Given the pressure that many companies are under to speed up their path to market strategies, accelerated approval in a rare tumour subset is one approach that can be considered.

It’s an exciting time in the field with the potential for several agents in development to move the needle and make a difference. I hope you enjoy this post, it was a real pleasure to talk with Dr Demetri again.

Subscribers can login below to read our interview with Dr Demetri at ECCO in Vienna.

Dr Nora Disis ECC 2015

Dr Nora Disis, U Washington

At the recent European Cancer Congress in Vienna, Austria, Dr Nora Disis  (pictured right) kindly spoke with BSB about her clinical research with avelumab (Merck KGaA/Pfizer), a cancer immunotherapy that targets the programmed death-ligand 1 (PD-L1).

Dr Disis (@DrNDisis) who is Editor in Chief of JAMA Oncology (@JAMAOnc) and a Professor of Medicine at the University of Washington, presented a poster at the meeting (Abstract #2749) with updated data for the phase 1b trial of avelumab in relapsed/refractory ovarian cancer.

In addition to reviewing the results with avelumab and in particular, the biomarker results for PD-L1 and CA125 expression, Dr Disis talks about why avelumab is different from other anti PD-L1 checkpoint inhibitors.

This is particularly important when considering a competitive and crowded marketplace where path-to-market strategies become more focused and critical.  Certainly some of the issues discussed in detail present a nice case study of some the challenges facing pharma companies when you are 5th, 6th or more to market.  Differentiation becomes a key driver that needs to be considered and incorporated into the clinical development plan.

She also talked candidly with BSB about some of the challenges and opportunities for checkpoint inhibitors and the PD-L1 in ovarian cancer, a disease where there is a high unmet medical need for effective new therapies.

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ECC Vienna Highlights Day 3Vienna, Austria: Yesterday at the European Cancer Congress we heard the latest data on checkpoint inhibitors. If there was any doubt as to the paradigm shift that immunotherapy is causing in cancer care, one only had to look at the full meeting rooms, and throngs of people trying to get into the IO sessions.

They were frequently standing room only with many people frustrated at being locked out or having to resort to the tiny overflow room.  Traditionally breast cancer has always been allocated the largest room for oral sessions, but with Immuno-Oncology increasingly drawing the largest and most enthusiastic crowds, this situation may well have to change in future years. It will soon be time for a specialist track on this topic in the biggest hall, making it easier for people to learn more about new developments across tumour types, rather than scatter them all over the program by organ.

The melanoma session yesterday, for example, was full to overflowing with every single seat snatched up.  Given the noise and crowds outside, the session start was delayed slightly as Prof Eggermont warmly and graciously invited people in to stand along the aisles and “engage in the debate from the sides.”  In a small packed room (why so small?!) this certainly added to the buzz and atmosphere.

One session Chair joked you only had to put “immunotherapy” in the title to ensure a great turn out. There were even people there until 7pm to hear the immunotherapy proffered papers yesterday, for example.

If I have one plea to cancer conference organisers it is to be more aware of the changing trends and enthusiasm – immunotherapy is the hottest topic right now and people want to hear about these agents irrespective of tumour type.  Why not have a two hour session on IO trials in the largest hall, almost like a special session so everyone interested can attend?  It makes a lot more sense than scattering the presentations all over the place and forcing people to run about the centre like rabid rabbits on too much caffeine!  It’s easy to cover 15K steps and over 6 miles trying to catch these studies in various sessions.

ECC 2015 Crowd OverflowAs you can see from the photo to the right, this is the growing crowd outside the bladder cancer session yesterday (I was one of them). People rushed from the atezo data in the lung cancer session to the bladder session down the other end of the corridor and were locked out due to a packed hall. They were frantically taking photos of Dr Rosenberg’s slides from the tv screens on the wall.

We have added some commentary and thought leader perspectives on the atezo data in the Day 2 highlights, for those interested.

It’s a particularly poignant scene for those of us who attended bladder cancer sessions only a few years ago where there were literally 12 men and a dog present in the hall.  How things have changed – IO fever has caught on even in this distant universe!

Meanwhile, the Day 1 Highlights and Day 2 Highlights posts have looked at the atezolizumab data in bladder and lung, as well as the nivolumab data in renal cell carcinoma and pembrolizumab in several different cancer types. There’s also some topline commentary on where cabozantinib fits in RCC.  Today’s highlights will probably be lung cancer focused with the latest nivolumab CheckMate 017 and 057 data being presented this morning.

In addition to the latest clinical data, there has been some scientific symposia at the meetings that have attracted experts well worth listening to.  More in future blog posts.

So what’s happening on Day 3 at the European Cancer Congress? This post highlights some of the sessions that may be of interest.

Vienna, Austria: it’s day 2 of the European Cancer Congress in Vienna (Twitter #ECC2015).European Cancer Congress Vienna

Along with 18,000+ attendees we’re looking forward to hearing about some more practice changing data.

Today in Vienna brings another busy and jam packed day at the European Cancer Conference (ECC).  We’ve already reached the point where the days blur and you have no idea which day of the week it actually is, you just follow the next fresh day in your personalised program or schedule.

So what’s in store today?

This morning brings updates on lung cancer, including the much anticipated atezolizumab results in POPLAR and BIRCH, as well as urothelial bladder cancer from the IMVigor trial. There is also a melanoma session that includes the oncolytic virus T-VEC, together with pembrolizunab and cobimetinib in separate study readouts. All this before lunch!

The afternoon promises to be equally interesting with an Immunotherapy in Cancer session that includes nivolumab, pembrolizumab plus we get our first look at a novel immunocytokine targeting CEA-IL2. A parallel session explores the science behind brain tumours with presentations on the tumour microenvironment, biomarkers and current trials.

In the meantime, the embargoes lift at 7am CEST on several studies including the atezolizumab data, which we highlight here.

To learn more about our insights throughout the day, including the latest immuno-oncology perspectives – some of which is potentially practice changing – subscribers can log-in or you can sign up in the box below.

After an entertaining morning yesterday – two interviews completed and wrong conference centre visited (yes really, there’s always a first for everything!) by lunchtime, things thankfully settled down.

Friday, for the uninitiated, is company symposia day – the equivalent of ASCO’s Super Friday. I rarely attend these in Europe, as they are more about corporate messages than what I call “proper CME”, meaning scientific or clinical fair balance and independence. This is one area where Europe still has a-ways to catch up the US on.

Before anyone gives me a hard time on this, I’ll never forget a vendor telling me a couple of years ago that I would love a particular symposia as he had personally ‘supervised and written’ the slides for the event, thus ‘ensuring’ it would be excellent while persuading me to attend against my better judgment. Naturally, I hated it – too many company messages or perspectives, and not ones I agreed with either – and left early, sadly disappointed.

We did attend the first ECC Press Briefing Friday afternoon with Drs Sant, Chouieri and Sharma. The last two authors presented on the metastatic renal cell carcinoma (mRCC) data after initial therapy, which is being presented in the Presidential Symposium on Saturday morning. It was quite an eye opener in many ways, with some subtleties well worth exploring in additional analysis and discussion.

Beyond the obvious highlights of the day for Saturday (nivolumab and cabozantinib data in mRCC), the first official day here is pretty jam packed with lots of other data to ruminate over.  Throughout the day, we’ll be adding additional notes, commentary and insights as the data emerges – and wifi permits.

To learn about our insights and thought leader perspectives of the relapsed/refractory mRCC data, subscribers can log in or you can sign up in the box to learn more.

Vienna Torte

Which of these cakes will you choose?

Greetings from Vienna where we are gearing up for our coverage of the European Cancer Congress (Twitter #ECC2015).

We’ll be writing a “highlights” post for subscribers at the end of the day here on Saturday, Sunday and Monday, then will follow- up with more in-depth coverage after we have talked with experts about the data presented.

Checkpoint Inhibitors and Cancer Immunotherapy are not surprisingly hot topics at the meeting.

In case you missed it, this month’s episode of Novel Targets (are we really on show #6 already?!) takes us on a new branch of the journey looking at various aspects of cancer immunotherapy:

Boosting T cell production – Stepping on the Gas

In past shows, we’ve looked at unlocking the brakes (checkpoint inhibitors), immune biomarkers (MDSCs and STING pathway), an inflamed or immunologic tumour type (lung cancer), a non-inflamed tumour type (prostate cancer), adoptive cell therapies and now it’s time for something really different… what happens when we literally step on the gas with immune agonists?

That’s the theme of the latest show – listen to Episode 6 on SoundCloud or iTunes (open access thanks to our sponsors, Genentech).

This article focuses on more detailed background and show notes for BSB subscribers.

It’s an important topic that is both simple in concept to understand and yet highly complex in terms of optimising therapy.

It’s time to take a deeper dive…

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Over the last couple of years we have heard much about targeting various checkpoints that exert an inhibitory effect on the immune system and the T cells, in particular.  The main targets where we have a growing body of evidence to date are CTLA-4, PD-1 and PD-L1, but there are others including LAG-3, TIM-3, ICOS etc.

Earlier this year at AACR, we saw new evidence that combining two checkpoints (anti-CTLA4 and anti-PD1) was superior to monotherapy in metastatic melanoma, albeit with a concomitant increase in toxicities.

What about the other inhibitory signals though?  Are they bystanders, much like passenger mutations that have little effect, or do they matter, at least in some tumor types?  If so, which ones?

We took a look at some of the emerging data associated with targeting TIM-3 – the results may well surprise some observers.

Several groups have banded together to produce the first CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (Twitter #cicon15) which focuses on the science underlying the immune system as it relates to cancer.  You can view the program agenda here.

These groups include the American Association for Cancer Research (AACR), Cancer Research Institute (CRI), Association for Cancer Immunotherapy (CIMT), the European Academy of Tumor Immunology (EATI).

We’ll hopefully be covering key abstracts at this event over the next few days and reporting on not only what the data is, but also the broader significance of the findings.

Dr Holbrook Kohrt StanfordHolbrook Kohrt MD PhD (pictured right) is a Stanford medical oncologist and clinical researcher who is leading the way in cancer immunotherapy combination strategies targeting CD137 (4-1BB).

He’s a speaker I greatly enjoy listening to at meetings. Earlier this year at The American Association of Immunologists (AAI) annual meeting (Immunology 2015) in New Orleans, he gave a noteworthy presentation on combination monoclonal antibody therapy.

The potential of a combination of an anti-CD137 monoclonal antibody such as urelumab plus an anti-CD20 such as rituximab, was one that he appeared to be particularly excited about.

Dr Kohrt kindly spoke with BSB and shared his thoughts on the potential of immune modulators, which instead of acting as inhibitors to “release the brake,” like checkpoint inhibitors, act as agonists to “step on the gas” and rev up the immune system. This is a concept that many Pharma companies are currently looking to explore for new drug development opportunities, for example:

Roche ESMO Media Briefing Immunotherapy Approach

Source: Roche Media Briefing at ESMO 2014 in Madrid

When it comes to combination strategies, the big unanswered questions are which ones will produce big gains in response rates and survival outcomes, and which ones will be duds?  

After all, much like targeted therapies, not all targets will be relevant in all tumour types – it will depend on the underlying immune system.

In New Orleans, Dr Kohrt talked about the potential advantages and concerns around combination strategies and why he’s particularly interested in CD137 as a novel target for immunotherapy.

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