First in class or best in class?
Which paths will ultimately lead to success with novel targeted therapies?
Ah this question often seems a perennial one to consider at AACR annual meetings – and this year is no different in this respect.
Personally, to me, it doesn’t really matter what you claim aspirationally based on preclinical or even early phase 1 dose escalation data because… a lot can happen between then and later registrational studies.
Think about it carefully – weak efficacy, wrong tumour selection or setting, adverse event profiles, even narrow therapeutic windows can all too soon interfere and play havoc like a wrecking ball with many a well intended clinical program, especially once you start looking at combination strategies!
No, it’s not as easy as it looks sometimes.
In our latest AACR Preview series, we take a look at a number of targeted agents in development, many aimed at novel targets at are not run-of-the mill…
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It’s time to talk about new developments in breast cancer.
@3NT with Dr Dennis Slamon at ESMO19
This week we will be featuring thought leader interviews with two breast cancer specialists as we look at new data in different subsets of this disease, in both early and metastatic settings.
We like to ring the changes with invited guests on BSB who comment on trial results and offer broader perspectives on their specialist field as well.
One expert is someone neither of us has ever interviewed before, while the other returns for an update on an early trial that is showing promise. Both interviews were conducted under embargo ahead of their presentations in Barcelona.
One of the myriad of challenges in oncology R&D is the tendency to begin exploration in the most advanced form of the disease with monotherapy to determine single agent activity and then work up to earlier lines of therapy with combinations evolving over time.
While it is always good to see proof that people are living longer with particular approaches, there is a real need to keep one’s eyes out on the horizon for new developments that may extend overall survival further.
What should those regimens look like and what are rational choices based on the underlying biology of the disease rather than being explored because that’s what a particular sponsor happens to have in their pipeline? We were delighted to have the opportunity for a much broader discussion some of these opportunities with today’s key opinion leader, Dr Dennis Slamon of UCLA, who presented data in an ESMO Presidential symposium and also talked about other topics in breast cancer research with BSB.
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Padstow, Cornwall – It’s May Day or ‘Obby ‘Oss, as it’s known locally in this little corner of south west England. The quaint festival means that it’s the biggest day of the year as over 30,000 people crowd into the tiny fishing village.
Obby Oss Blue
Centuries old traditions are still alive and well in this part of the country and the big question of the day (are you red and white or blue and white?) is a far cry from the complex high tech world of cancer research.
Still, with all the time and attention focused on immunotherapy and targeted therapies of late, it is all too easy to forget what’s happening on the epigenetics front, which is quite a bit in practice.
We often see random allcomer approaches to clinical trials, which are find for phase 1 studies where you want to gather data on responders and non-responders in order to conduct PK/PD and immune profiling, as well as biomarker and signature development, but a potential recipe for disaster in phase 3 if you have no idea exactly what’s driving the efficacy since you can all too easily end up with unbalanced arms that you didn’t control for and thus skew your survival curves in a way you didn’t anticipate.
Why on earth would you use a targeted therapy in an untargeted fashion? Hmmm obvious question and yet, many companies still do this all the time.
There are some biotechs out there, I’m pleased to say, who do conduct extensive translational and biomarker research. Obviously finding those markers is a lot more tricky than choosing red or blue.
One biotech company we have been keenly following for a while is Syros.
We first wrote about them in Spring 2014 and now, five years on, I thought it would be a nice idea to catch up with one of their founders and learn more about the science underpinning what they’ve done and where they’re going with future projects. Not only do they invest in smart medicinal chemists, profiling and translational research, but they also seek to identify rational reasons why people respond to their compounds.
The answers were rather interesting and there’s quite a bit that readers might be curious to learn more about…
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San Antonio – As the Fall conference season is rapidly drawing to a close, it’s time to highlight some key findings on breast cancer from the San Antonio Breast Cancer Symposium (SABCS).
In this in-depth post where we explore the breast cancer landscape in terms of updates on key trials that stood out as well as highlights from several thought leader interviews on translational and clinical aspects of the disease.
We also explore some important biological and biomarker aspects to think about in future IO trials.
Are you ready? Let’s roll!
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View from Stars and Stripes life guard hut on Miami Beach
Our latest article is part Journal Club entry for August, part look back at some data from AACR and ASCO plus a part look at a relatively new target from an obscure biotech that caught my attention recently.
To do this, we pose three critical questions and attempt to answer them.
The targets and markers chosen for review here may well surprise a few people.
If we want to understand how to help more people respond to cancer immunotherapy then we need o understand the underlying biology and the tumour microenvironment in greater depth than we currently do.
Gradually, we are getting more clarity on a few areas as new data is being published…
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Picking a PARPi – what can the biology tell us?
One of the really interesting questions I recently received from a BSB subscriber related to PARP inhibitors – they asked whether the therapies are all the same and can be considered interchangeable as a class?
Around the same time, another reader wrote in asking if there was any new information on what’s happening with PARPi combinations in breast or ovarian cancers?
This got me thinking as there has actually been some useful preclinical and clinical studies reported on both fronts that at least begin to open our eyes to new information based on research that has been reported in several places.
Thus I thought it would be useful to summarise the data and take a look at what we learned in the process.
Fair warning – some of the findings turned out to be a little bit more surprising than you might normally expect to see…
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It’s one of those truly crazy busy times of the year with no less than three cancer conferences going on this week alone in different cities and time zones. I’ve also been busy scheduling and conducting phone interviews for these events. More than once have I dialled the wrong number or access code or got briefly confused by time zone changes (CT and CEST?!) and misread the interview at the wrong time… and was that 4.30pm ET or CT?
River Walk, San Antonio, Texas
One of those… If it’s Tuesday it must be Belgium moments to be sure.
Thankfully, everyone has been very thoughtful and helpful and I haven’t managed to get the expert names incorrect (yet)!
Today, I want to take a break from the ASH17 coverage and switch horses from hematologic malignancies to breast cancer and from Atlanta to San Antonio, as there is some important new data emerging from the Lone Star state.
In particular, one of the top posts of 2016 on BSB was on CDK4/6 inhibitors so it’s time for an update on this and some other key studies!
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Recently there has been a glut of encouraging new research published on the topic of breast cancer that is well worth perusing as a group, since new combination studies may emerge from these kind of data.
In this month’s Journal Club edition, we explore five such articles plus some related research in support of the main themes.
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Churchill College, Cambridge: Yesterday, the main focus at the EACR Cancer Genomics conference was on immunology-related topics as they pertain to genomics.
A rainy day in the Fens for #CG17
Unfortunately, however, the Great British summer ended as almost as soon as it started – I can confirm that it started on a Wednesday this year and fizzled out by the following Tuesday!
Consider that on the first two days of the conference it was gloriously sunny and those wooden benches were full of scientists sitting outside eagerly discussing their research or various collaborations afoot.
A mere 24 hours later, the heavens opened and steadfastly drizzled all day long, much to the chagrin of the attendees.
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#ASCO17 Poster Hall aka rugby scrum
There were a lot of gems in the poster halls at ASCO this year, a fact that is partly a reflection of the wealth of new data with various IO combos and also the early cutoff date.
Now I jested before the meeting that these sessions were akin to a rugby scrum and lo and behold (see photo right) they were even more jam packed than usual!
If you wanted to best the eager and energetic Wall St analysts then remembering your ruck and maul skills were not a bad thing to have in muscle memory… It was not something I attempted in the Go-Cart this year for fear of bowling people over in the stampede to nab the QR codes 🙂
Much of the previous readouts have been with monotherapy in immunogenic tumours such as melanoma, lung, bladder, gastric, renal cell carcinoma etc. Objective response rates in metastatic triple negative breast cancer (TNBC) have generally been under 20%, however.
Lately, the focus has turned to the deepening of responses in these tumours with various combination approaches and also moving earlier in the disease setting, where immunotherapies might be expected to be more effective with a lower tumour burden.
While in Chicago, we spoke to a breast cancer specialist about where IO combos are going and his thoughts on future opportunities in our third post in a series on various aspects of new developments in breast cancer.
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