Biotech Strategy Blog

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

With the recent approvals of nivolumab (Opdivo) and pembrolizumab (Keytruda) in advanced lung cancer as well as new checkpoint inhibitor data presented on atezolizumab at the European Cancer Conference in Vienna, there are several new lung cancer immunotherapy controversies to consider such as…

  • How do we choose between docetaxel chemotherapy versus anti-PD1/PD-L1 immunotherapy?
  • Which checkpoint should we choose?
  • Is the PD-L1 biomarker useful and important?
  • Do the company assays differ?
Dr Jack West

Dr Jack West

Dr Jack West (Seattle) got the ball rolling on some of these issues earlier this month, generating quite a spirited and useful debate on Twitter, demonstrating that clinical decisions in this area are not as cut and dried as many might think.

In addition, we spoke to a number of lung cancer experts in Vienna for their perspectives on the data, the biomarkers, treatment paradigms and other critical issues.

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For some time now there has been much debate about finding a predictive biomarker of response for EGFR monoclonal antibodies used in the treatment of advanced colorectal cancer.  These include cetuximab (Erbitux) and panitumumab (Vectibix).

After all, we know that they tend to work in wild type disease (as shown in the US label below) and that KRAS and NRAS mutations on codon 12 and 13 on exon 2, as well as others on exon 3 and 4 tend to portend resistance to therapy, but beyond that not much is known.

Cetuximab v2

At the European Cancer Conference in Vienna last month I was intrigued to see some new data emerge that may help researchers better understand and predict which people with metastatic colon cancer are more likely to respond in the future.

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ECC 2015 Dr Sandra Demaria Radiation Immunotherapy Title SlideAt the recent European Cancer Congress in Vienna, one of the Immunotherapy in Cancer Scientific Symposia that caught my attention was on Combining Radiation and Immunotherapy.

When it comes to immuno-oncology, it’s a topic we’ve not heard that much about, although many trials in combination with radiation are planned or in progress.

In the symposium, Dr Sandra Demaria (Weill Cornell Medical College) gave a presentation entitled: “Molecular Basis for Radiotherapy in Synergy with Immunotherapy.”

What are the new concepts on how to combine radiation with immunotherapy?

Dr Demaria shared her thoughts with BSB; excerpts from the interview are included in the following post along with additional commentary.

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At the European Cancer Conference (ECC 2015) held in Vienna recently, a number of promising targets emerged along with new drugs in development in several different tumour types.  Not all of them were from big Pharma – some were from up and coming young biotechs that will be worth watching out for.

Austria SchnappsIn this first part of our ‘New Drugs on the Horizon’ mini series, we chose four interesting and largely positive studies to highlight and discuss in-depth.

In the past, there were many negative trials to pick over and ponder why they didn’t quite pan out.  After all, it’s relatively easy to be an armchair critic and hindsight is a wonderful thing.

Picking only four from the many promising choices of trials presented this year available turned out to be quite hard given there were many that caught our attention – a bit like choosing only one of four out of the many schnaps to sample locally!

Today’s review looks at four very different drugs and approaches in early development from Pfizer, Stemcentrx and Ignyta – they include encouraging early data on both small molecule tyrosine kinase inhibitors (TKIs), as well as antibody drug conjugates (ADCs).

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On Friday last week, AstraZeneca confirmed that their combination trial for osimertinib, as it’s expected to be called or AZD9291, as it’s more commonly known (anti-EGFR mutant, T790M inhibitor) plus durvalumab (MEDI–4736, anti-PD-L1) in non-small cell lung cancer (NSCLC) is on clinical hold following an increase in ‘interstitial lung disease-like reports.’

As companies with checkpoint inhibitors and other immunotherapy agents expand beyond monotherapy into logical combinations, is the risk of increased ILD from combining an EGFR inhibitor with a checkpoint something other companies need to watch out for?

By the way, we strongly disagree with the reported conclusion of Goldman Sachs on this issue – and here’s why…

Today’s article explores this controversial issue in more depth.

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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.

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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.

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