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At the 2016 San Antonio Breast Cancer Symposium (#SABCS16) one of the mini-symposia that caught my attention was on “Harnessing the Immune System in Breast Cancer.”

A line-up of top researchers and clinicians shared the latest on breast cancer immunotherapy:

  • Laurence Zitvogel MD PhD (Gustave Roussy), “From Breast Cancer Surveillance to Immunotherapy
  • Leisha Emens MD PhD (Johns Hopkins), “Breast Cancer Immunotherapy: Building on Clinical Success”
  • Andy Minn MD PhD (Univ of Pennsylvania): “Identification of Resistance Mechanisms to Checkpoint Blockade for Cancer”
Dr Laurence Zitvogel SABCS16

Dr Laurence Zitvogel at SABCS16

Readers of the blog will recall we last spoke with Dr Emens at the AACR 2015 annual meeting (is it really that long ago?!) where she presented the first data for the PD-L1 checkpoint inhibitor atezolizumab in Triple Negative Breast Cancer (TNBC). See post: “Checkpoint data rocks AACR 2015.”

You can also hear Dr Emens talk about the data on Episode 1 of the Novel Targets Podcast.

What’s new in breast cancer immunotherapy and how have things advanced since then?

At SABCS16, we heard about a novel immunotherapy strategy targeting adenosine in breast cancer, and the trial with an adenonsine antagonist, CPI-444 (Corvus Pharmaceuticals, NASDAQ: CRVS) that’s now underway.

Last September, Corvus senior scientist Stephen Willingham, PhD and Chief Business Officer, Jason Coloma, PhD spoke to BSB about the data they were presenting at the 2016 CRI-CIMT-EATI-AACR Cancer Immunotherapy Conference in New York. See post: “Corvus moves fast to target the tumor microenvironment and improve checkpoint responses.

Corvus had a presentation at the 2017 JP Morgan Healthcare conference (#JPM17) yesterday, and we’ve included some additional commentary on that in this post.

After the SABCS16 cancer immunotherapy mini-symposium, Dr Leisha Emens, Associate Professor of Oncology at the Johns Hopkins School of Medicine, kindly spoke to BSB.

Dr Leisha Emens SABCS16

Dr Leisha Emens at SABCS16

She’s one of the rock stars of breast cancer immunotherapy, and it was truly a pleasure to catch up with her again in San Antonio.

This is the second in our series of expert interviews from #SABCS16. In case you missed the prior posts and want to bookmark for the upcoming ones, you will find them on the conference page (Link).

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We’re kicking off the first in a mini-series of expert interviews from the 2016 San Antonio Breast Cancer Symposium #SABCS16 with a leading researcher who has discovered a first-in-class compound that shows preclinical promise in several cancers including multi-drug resistant metastatic breast cancer.

It has a novel mechanism of action: 

“Interestingly, it was the only molecule, out of the 150,000 we screened that seemed to work through this pathway.”

To go from “bench to bedside,” and take this drug into the clinic now requires funding beyond what academia can provide.

If you’re at #JPM17 and into early stage VC funding or are in pharma/biotech business development BD&L and are on the look out for an innovative new licensing/investment deal, this post is for you.

What makes this a great story is I heard that one “missing piece of the jigsaw” in working out the pathway through which the drug worked came from unrelated research presented at a seminar on wound healing in zebrafish!

As a 2013 article by Robin McKie in The Observer notes, zebrafish (Danio rerio) share 70% of our genes, which makes them pretty cool research models. They are also transparent.

Hearing this anecdote reminded me of my conversation with Dr William Pao that you can hear on Episode 3 of the Novel Targets Podcast where he astutely said:

 “You never know where things are going to lead, you just have to be able to take advantage of them.”

That could also be a metaphor for life.

Science is about making sense of connections and patterns, which is why funding of basic science is so important. A piece of work by one researcher can unlock a breakthrough by another in a totally unrelated area.

While I was doing this SABCS16 interview, I was also reminded of the story behind the development of enzalutamide, and how AACR past-president Dr Charles Sawyers pitched his UCLA drug discovery work to several major pharma companies, without success, until Dr David Hung at Medivation took the risk… and the rest is history.

What makes that story so surprising is at the time Dr Sawyers already had a track record of success with his work on the development of imatinib!

It was a privilege to talk with a senior scientist at #SABCS16 who has thought outside of the box, made scientific connections, and in the process developed a new drug that shows exciting preclinical promise.

Improving the outcome for cancer patients requires the translation of basic science into new products that enter clinical trials.

I do hope funding will be forthcoming to move this first-in-class drug into the clinic so that’s its potential can be fully evaluated.

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If you’re at #JPM17, it’s a great time to buy a sub to BSB and put it on your expenses!

John P. Leonard, MD is the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell in New York. He’s a Lymphoma specialist.

Dr John Leonard at ASH16

Like many hematologists, he’s embraced Twitter as way to share his expertise with others in the hematology community. You can follow him at @JohnPLeonardMD.

Over the last couple of years prior to the ASH annual meeting, Dr Leonard has highlighted 10 lymphoma abstracts that caught his attention. You can tell he gets excellent social media pickup by the fact he’s even generated a hashtag to make them easy to find: #Leonardlist and other hematologists generate conversations around his eagerly awaited picks:

In case you missed them on Twitter, and in the spirit of David Letterman, Dr Leonard took me through this year’s #LeonardList and thoughtfully explained in detail why each selection made the cut… for oncology watchers, the why is often more important than the what.

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Like migrating birds, the San Antonio Breast Cancer Symposium (SABCS) has many regular attendees who return each year to enjoy the location and opportunity to hear about latest advances in breast cancer. One leading academic clinician told me she’d been to every meeting for the past 20 years.

The Alamo, San Antonio TX

The Alamo

SABCS offers a unique mix of academic and community doctors, translational researchers, basic scientists and patient advocates. The only downside is that at times the meeting (to an outsider) does feel like a club or family with it’s own idiosyncrasies.

This year, a leading breast cancer oncologist characterized the meeting to me as a “negative one,” meaning several clinical trials were presented that reported essentially negative results.

Although these are an important part of science, and it was good to see them presented, like most of the media, even medical oncologists want to see the “positive” news and that’s understandable. There was no practice changing phase 3 data as in previous years. The trial we most anticipated being at SABCS was delayed due to slow events and that’s a good sign as it most likely means women are living longer…

As readers of the blog will know, we’ve yet to find a medical/scientific meeting that did not offer up pearls, and #SABCS16 was no different in this regard.

Whether you have to spend time in the poster halls or go to obscure sessions, they are there to be found somewhere.

I came away from #SABCS16 with fresh insights into new targets, biomarkers, and also how the world of cancer immunotherapy will interface with genomics. It is these advances in basic and translational science that drive future clinical research.

Experts I spoke to at San Antonio were generous with their time and insights and we’ll be rolling out a series of thought leader interviews in Q1, 2017.

In this post, I wanted to set the scene with what I thought were 3 trends emerging from SABCS16. This is of course, an entirely subjective choice and if you went to the meeting, and/or are an expert in the area, your list would most likely be different.

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If you’d like to buy a quarterly subscription as a gift for someone, do contact us and we can arrange for it to be set up to run from the New Year in the recipient’s name.

The 2016 annual meeting of The American Society of Hematology (ASH) is rapidly approaching and starts later this week on Friday in San Diego (Twitter #ASH16).

ASH15 Late Breaker Session“Super Friday” at ASH, as it’s commonly known, is a day typically associated with satellite symposia, where company’s and organisations sponsor or give unrestricted grants for continuing medical education (CME) around a specific topic or theme. These are professionally produced events that offer fair balance and a line up of experts.

There are also scientific workshops and unofficial meetings not part of ASH….so if you have plans to be in San Diego on Friday where should you be? 

I’m flying in late Thursday and have carefully reviewed all my options for Friday, of which there were many.

ks-beerdetail-2016-03-rtaOne now jumps out to me as a “must attend” and I’m afraid it’s not drinking a Red Trolley…. You’re welcome to join me or can maximise your mileage by going to another event and avoiding duplication of coverage.

Tomorrow @MaverickNY will be kicking off her coverage from Munich and the EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium (Twitter #ENA2016) before flying to San Diego on Friday.

If you’re hoping for coverage of World Lung from Vienna, I’m afraid that fell through the cracks thanks to it’s change of date from September to December and the clash with ASH who always hold their annual meeting around the same time.

After #ASH16 I’ll be doing the “on, on, on” to San Antonio for #SABCS16. It’s going to be a busy 2 weeks!

Happy Cyber Monday! Subscribers can login to read my ASH16 Super Friday Preview or you can purchase access below. 

Copenhagen – Day 3, Sunday at #ESMO16 was a day to remember on many levels. From being carried forward by a rush of people as a massive crowd was finally let into the Presidential Symposium…

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

…to hearing an outstanding discussion of data by one of Europe’s leading lung cancer experts, Professor Jean-Charles Soria (@jsoriamd). He was insightful, engaging, as well as funny in places and was a hard act to follow…

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

The end result was a day to remember, most significantly it was one where we heard data that will change the standard of care in front-line non-small cell lung cancer (NSCLC), with the expected approval of pembrolizumab (Keytruda) for patients whose tumors have a high expression of PD-L1 (50% or more).

We’re continuing our daily digest of highlights from sessions we attended at the 2016 European Society for Medical Oncology (ESMO) Congress here in Denmark.

nyhavn-denmark

The sun has not shone much here in Denmark during the Congress, the above photo of Nyhavn was taken just before the meeting started, but the data at ESMO16 has shone brightly with two more publications online in The New England Journal of Medicine to coincide with their presentation in Sunday’s Presidential Symposium:

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer (NEJM link)

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck (NEJM link).

This mini-series of daily digests over the 4 days of the Congress is intended to give subscribers a finger on the pulse on some of the buzz and conversation…. and occasionally an alternative perspective. We’ll be writing more detailed posts as part of a post-conference series.

In this post, @MaverickNY offers her topline impressions of the lung cancer data presented in the Presidential Symposium, how this will change how some patients are treated, and the resulting impact on the lung cancer landscape. Cancer Immunotherapy continues to drive changes in clinical practice, and is doing so at a very remarkable pace.

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Copenhagen – it’s the end of Day 2 of the European Society for Medical Oncology (ESMO), which this year had a record-breaking 20,239 attendees.

esmo16-posters

Three of the presentations in today’s plenary Presidential Symposium were simultaneously published in The New England Journal of Medicine – I haven’t seen that happen before.

All three were also featured in this morning’s media briefing in Copenhagen.

  • Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (NEJM link)
  • Prolonged Survival in Stage III Melanoma with ipilimumab Adjuvant Therapy (NEJM link)
  • Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer (NEJM link)

In today’s daily digest there’s top-line commentary and insights from some of the sessions we attended. In a separate post, we have already discussed the niraparib data.

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Copenhagen – PARP inhibitors are creating quite a lot of controversy here at the 2016 ESMO Congress.

Yesterday, we heard the data for rucaparib (Clovis Oncology) as monotherapy treatment for the advanced ovarian cancer patients with BRCA mutations who have been treated with 2 or more chemotherapies.

In a totally different ovarian cancer indication, today at #ESMO16 we heard the results of the phase 3 trial for niraparib, the PARP inhibitor from Tesaro, that many thought was superior to the rucaparib data, ignoring the fact you can’t make comparisons for maintenance versus relapsed/refractory treatment.

The niraparib ENGOT trial was presented in today’s plenary Presidential Symposium by Dr Mansoor Mirza and simultaneously published in The New England Journal of Medicine (link). It was also featured in a media briefing earlier today in Copenhagen.

esmo-2016-press-briefing

In this piece we’ve taken a critical look at the Tesaro (NASDAQ: TSRO) niraparib data and the controversial claim made by their principal investigator, Dr Mirza, that the data shows there is no need for a companion diagnostic to be associated with this drug.

In other words, the intent that regulatory approval will be sought for this drug as maintenance therapy for platinum-sensitive ovarian cancer patients, irrespective of whether they have a BRCA mutation or homologous recombination deficiency (HRD).

This post provides commentary on this and offers the perspective of a leading ovarian cancer expert with deep experience of companion diagnostics in this field.

Subscribers can login to read what Tesaro aren’t saying about the Niraparib data or you can purchase access below…

Copenhagen – today was day one (Day 1) of the 2016 Congress of the European Society for Medical Oncology (Twitter #ESMO16).

esmo-2016-registration

ESMO 2016 Registration

The meeting is a few weeks later than last year’s European Cancer Congress in Vienna, and it definitely feels as though autumn has arrived in Europe.

copenhagen-cycling

Cyclists in Central Copenhagen

This year we’re providing a daily digest at the end of each day at ESMO 2016 in Copenhagen.

The aim is to provide some top-line commentary around the sessions we attended earlier in the day. Think “Match of the Day” for those in UK or “Sports Center” for those in the US. We’ll be writing more in-depth pieces after the meeting.

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Cancer Immunotherapy will require personalized treatment based on the type of cancer you have, and the immune response your body has generated to the cancer.

Dr Holbrook Kohrt Stanford

Dr Holbrook Kohrt at Immunology 2015

The sadly missed and visionary Dr Holbrook Kohrt was very prescient when he told BSB in New Orleans back in May 2015:

“Today when I see a patient or you go to a cancer center, the first thing they ask is what type of cancer do you have? Most patients respond – breast cancer, a colon cancer – unfortunately we are not in position where patients can say I have a deficiency in my cytotoxic CD8 cells or I have overly active regulatory T cells.

I actually envision a day when patients will know both sites, they will know they have breast cancer and they’ll also know it’s because there’s a lack of effector cytotoxic CD8 T cells. That combination knowledge, of what your immune system is lacking and what tumor you have, that combination will allow you to identify what type of immunotherapy you need.

Patients may need CAR directed T cells and those will be for patients who have completely non-functional T cells themselves, no matter what therapy you give them, you’re not going to create those cells within the body, therefore you need to do it ex-vivo in a petri dish and give it back to them.

Other patients may have T cells that just need to be turned on and so all they need is a checkpoint modulator and that combination is going to be effective enough for them.

So it’s this dual diagnosis, diagnosing their immune system and diagnosing their tumor that’s going to allow us to identify one, two, or three therapies that’s going to be the right cocktail.” 

See post: Holbrook Kohrt leads the way in Targeting CD137, you can also listen to excerpts on the Novel Targets Podcast: Episode 6: Stepping on the Gas

ICYMI do listen to the tribute to Dr Kohrt on the Novel Targets Podcast from two people who knew him at Stanford: Dr Ron Levy and Dr Dan Chen (@DanChenMDPhD). It’s at the start of Episode 11: Cancer Immunity Cycle.

Immunoscore® — a diagnostic test based on the immune profile of a patient is based on the pioneering work of INSERM scientist Dr Jérôme Galon.

Dr Jerome Galon at ASCO 2016

Dr Jérôme Galon at ASCO 2016

We are fans of his work, and interviewed him at the 2015 European Cancer Congress. See post: Immunosurveillance, Immunoscore & Personalized Cancer Immunotherapy – an interview with Jérôme Galon.

Over 10 years ago, Dr Galon’s research published in The New England Journal of Medicine and Science showed that the type, location and density of immune cells within a tumor predicts clinical outcome in early stage colon cancer.

These findings led to the development of an assay called Immunoscore® that’s based on an analysis of cytotoxic T cells, the ones that kill cancer.

In the process, it has led to a new way of classifying stage 2/3 colon cancer patients: those with a high Immunoscore® (good prognosis), and those with a low Immunoscore® (poor prognosis). Dr Galon’s work has shown that irrespective of whether you are MSI high or MSS, colon cancer prognosis correlates with Immunoscore.

Dr Bernard Fox at #AACR16

Dr Bernard Fox at AACR 2016

As we heard from Dr Bernie Fox (@BernardAFox) at AACR 2016. See post: AACR Cancer Immunotherapy Insights from Dr Bernard Fox, listen to excerpts on Novel Targets Podcast Episode 12: Of Mice and Men:

“What I teach the first year medical students is that if you have metastatic cancer, the only thing that makes a difference in your life is whether you’ve got your immune system turned on. If it’s not turned on, it doesn’t make a difference what you get, chemo, radiation, surgery, you aren’t going to do well.”

Immune response is key to outcome, which means that knowing what your immune profile is will be key to deciding which of the many immunotherapy options, either alone or combination will achieve the desired effect.

A large multinational phase 3 clinical trial sponsored by the Society for Immunotherapy of Cancer (@SITCancer) was set up to validate Immunoscore® as a biomarker in Stage 2 colon cancer.

Dr Galon and co-authors reported the results at ASCO 2016. See post: immunoscore validated as an important biomarker for colon cancer. He featured on the ASCO 2016 episode of the Novel Targets Podcast: Immunotherapy or Bust.

Immunoscore® is now being commercialised by Marseille based HalioDx(See post: HalioDx CEO Vincent Fert outlines commercial strategy for Immunoscore in US and Europe).

ciml40During a recent visit to the Marseille Immunopôle for #CIML40, I had the pleasure to do an impromptu tour of the HalioDx lab.

When listening/watching this, do bear in mind this was not a scripted tour, and also the people I spoke to were speaking English as a second language.

It’s not intended to be a definitive guide; if you are a patient you should talk to your doctor about any questions you have about diagnostic assays such as Immunoscore.  At the moment, it’s only available for research or clinical trial use, but HalioDx has plans to make the assay commercially available on the US and Europe.

The company has more information on their website and also recently published a paper in the Journal for Immunotherapy of Cancer (open access) that describes how the test is done in more scientific detail.

In the meantime, subscribers can login to join me for a lunch-time tour, or you can purchase access below. The audio-slideshow tour was for several weeks open access and available to all, but is now for subscribers only:

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