It was only five years ago that the number of abstracts on CAR T cell therapies at the American Society of Hematology (ASH) ran to a dozen or less. Fast forward to 2016 and we now have tens of them, almost too many to count, let along review quickly and easily.
A scene from ASH 2015…
To give you an idea of the staggering speed of progress, in 2010 it took me less than half an hour to search and read all the CAR T cell abstracts, now it takes nearly a whole day to peruse and review them carefully.
We can’t resist a challenge…
As usual, we will write in more depth from the meeting as the data emerges in real time since many of the abstracts are often placeholders with updated information provided at the conference itself.
For now, here we provide an in-depth preview of the CAR T cell landscape in terms of the players, the products, new scientific research, biomarkers, emerging trends and more in a handy What to Watch For (W2W4) guide on key areas to expect at ASH to enable better enjoyment and awareness as the data rolls out next month.
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There was a time when it seemed that all the good news emerging in cancer research was on breast cancer, that is clearly no longer true as other tumour types have seen some leaps and bounds with different modalities, including areas previously thought to be a graveyard for big Pharma, such as metastatic melanoma, for example.
New Dawn at the Houses of Parliament
That said, after the excellent developments in hormone-sensitive disease and the identification of the HER2 oncogene, we now have CDK4/6 as a validated target in metastatic breast cancer.
Pfizer’s palbociclib (Ibrance) lead the way, with two approvals in previously untreated and relapsed ER+ HER2- advanced breast cancer. Two other companies in this field are Novartis with ribociclib and Lilly with abemaciclib. Data is being presented on all three therapies at ESMO this year.
In addition, there are some other abstracts of note that are well worth discussing.
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In our ECCO Preview series last year (note: ESMO and ECCO have alternated the EU major cancer conference in the Fall for years), we highlighted several promising novel agents in development including the following:
- StemCentRx’s anti-DLL3 inhibitor: rovalpituzumab tesirine (ROVA-T)
- Ignyta’s Pan Trk, ROS1 and ALK inhibitor: entrectinib
- Pfizer’s anti-NOTCH3 inhibitor: PF–06650808
- Pfizer’s PTK7 ADC in TNBC: PF–06647020
What happened to them all? Were they good selections or not?
Well, AbbVie acquired StemCentRx in a $10.2B deal, Ignyta are busy advertising their new clinical trial enrollment for entrectinib as a non-chemotherapy and non-placebo controlled study on social media, suggesting that compound’s clinical development is still very much alive, while both the Pfizer compounds are also still active, as far as I know.
None have yet been consigned to dog drug heaven, which is quite something considering the failure rate in oncology drug pipelines!
Indeed, last year the Pfizer PTK7 ADC data was focused on triple negative breast cancer, where there is a solid rationale. This time around, the same research group explore the latest activity in advanced solid tumours, including ovarian cancer, as mentioned in the earlier Preview (See: 9 key abstracts in Ovarian Cancer).
So it’s time to sit down and chew the fat on one of my favourite topics at conferences – Development Therapeutics.
Here we consider which other compounds – other than the Pfizer ADC – that are worthy of highlighting and watching out for this year?
There are certainly some curious and quite different (i.e. novel) approaches to look at.
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If you had told me several weeks ago that we would write over 28 posts on #AACR16 and become very interested in mouse models, then most likely I would have laughed out loud and told you not to be so ridiculous! Here we are with the 29th one and, another, on the bromododomain landscape yet to go. Such was the vast richness of data and concepts being discussed or presented in New Orleans for those who chose to look.
Today, I want to start the segue from AACR to ASCO coverage.
One way to do that is through the second part of the Gems from the Post Hall series. This latest one looks at a range of intriguing new targeted therapies and novel targets that are emerging, including a pharma company with a particularly interesting early pipeline.
Several pharma companies presented interesting data on their very early compounds currently in development, plus I noticed a trend for a new class of targeted therapies to emerge, MNK inhibitors, which we will also discuss.
Companies mentioned: Bayer, Orion Pharma, Lilly, Novartis, Pfizer, Agios.
Targets mentioned: PI3K, CDK, Akt, TWEAK, FGFR, BUB1, IDH1, SMYD2, MNK
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It’s Tuesday at the 2016 JP Morgan Healthcare conference in San Francisco (Twitter #JPM16).
Each day of #JPM16 we’re doing a rolling blog post which we’re updating throughout the day with commentary and insights on the company presentations we’re covering.
While we’re not giving a blow-by-blow account, many companies have the slides readily available, we will be commenting on noteworthy news, and what we learn about corporate strategy going into 2016.
For those of you who like to catch up with the final summary of each day’s highlights, you can read yesterday’s Day 1 synopsis here and our interview with Seattle Genetics CEO, Clay Siegall here.
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There are now several CD40 agonist antibodies in early clinical development from several different companies, including:
- Roche – RO7009789
- Apexigen – APX005M
- Seattle Genetics – SEA-CD40
- Alligator Bioscience – ADC–1013
This post is the last in our cancer immunotherapy coverage from the European Cancer Congress in Vienna. It features excerpts from an interview with Dr Christian Rommel, head of oncology discovery at Roche in Basle, Switzerland in which he talks about the development of their CD40 monoclonal antibody. Readers may recall we wrote about this from SITC 2014 last year: “Targeting CD40 in Cancer Immunotherapy.”
This post is also a new primer on CD40 as we start our coverage of the Society for Immunotherapy of Cancer (SITC) 2015 annual meeting. We’re informed by SITC it’s a sell out conference with 600 more people than last year’s record breaking number. Cancer Immunotherapy is indeed the hottest topic in cancer drug development.
If you have plans to be at National Harbor this week, we hope to see you there!
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.
In 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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We know from preclinical research that immunosuppressive tumour microenvironments can restrain anti-tumour immunity, thereby making subsequent therapeutic interventions less effective than expected. CD40 activation has been shown to reverse immune suppression and drive antitumor T cell responses, which in turn could lead to potentially better outcomes.
What happens when patients with advanced melanoma are given a checkpoint inhibitor plus an immune agonist such as anti-CD40?
Can we help the non-responding patients to checkpoint blockade improve their outcomes and shift the long tail in survival curves up using this approach?
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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?”
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.
To 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.
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It’s a while since we discussed ALK+ lung cancer, but with new data coming out at ESMO last week, this is a good time to take stock and see what’s happening with the next generation inhibitors in a post crizotinib (Xalkori) world. These include ceritinib (Zykadia), alectinib and Ariad’s AP26113, which just received Breakthrough Therapy Designation from the FDA.
At ESMO two years ago in Milan, it was quite clear in a dedicated ALK session that these agents not only looked very promising, but were also likely to be fast tracked to market in patients with crizotinib resistance. All are more potent (based on the IC50) than crizotinib, while some target point mutations associated with crizotinib resistance and others have activity in patients with brain metastases, which is one of the common causes of progressive disease with crizotinib.
Today’s post is a long and meaty one – it not only covers data that was presented at the meeting, but also offers a glimpse into the changing ALK landscape.
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