Scaling the ramparts in Real Madrido
It feels slightly surreal to be writing about this year’s annual ESMO confab instead of attending in person in Madrid, Spain.
While much of the time and attention at ESMO is usually focused on the major phase 3 readouts from various clinical trials, we will be covering these during the meeting as they are presented to avoid repetition since many of the topline company trial results have already been announced.
In this year’s conference Preview series, I wanted to take a step back and explore early new product development in several forms:
- Biomarkers and potential new ways of predicting outcomes in development
- Emerging novel targets of interest
- Developmental therapeutics – trials and tribulations
This initial review will tackle some important developments pertaining to various biomarkers of interest.
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George Martin’s quote seems rather apt this morning as NextCure announced there was disappointing single agent activity with their Siglec–15 directed agent (NC318) in an ongoing phase 1/2 trial.
There were a couple of initial partial responses reported at SITC last year and now it may seem as if the wheels are falling off the wagon.
What can we learn from the latest update?
It turns out quite a bit…
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Looping across different types of analyses can yield intriguing and unexpected results
Not in Chicago – It still feels surreal not to have been to windy city and back for the annual meeting at ASCO this year, such was the ongoing effect of the pandemic in the oncology world.
That said, the virtual meeting has produced some gems this year, including some very important findings many may have missed.
In our latest post meeting report we focus on both biomarkers and clinical findings.
We look at how there are various elements may interplay in unexpected ways, whether signatures from one trial are helpful in another, are there likely to be changes in treatment patterns as a result of data presented and where some emerging early signals might be useful.
One other aspect which crossed my mind was how a deep scientific approach used in one particular cancer might have potential applications in other tumour types with few somatic mutations present such as TNBC, prostate cancer or soft tissue sarcomas.
The results might produce quite different results, yet the process itself might be rather useful to consider…
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Part of the next wave of early immuno-oncology agents are focused on addressing the tumour microenvironment and inhibitory factors that dampen down immune responses.
As we look at all the options available, there are a few obvious ones such as physical barriers and inhibitory cytokines or chemokines, but beyond that are a vast array of other potential targets we can aim at therapeutically.
We have covered quite a few of these already, but here’s a new one to add to the list.
One particular advantage is that because it is early in development, few competitors have cottoned on to the concept yet. First mover advantage can have quite a few benefits, after all.
Here’s an important question to consider in terms of oncology R&D – would you rather explore a blue ocean strategy or follow the lemmings off the cliff and be 14th to market in a highly competitive red ocean?
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Some of the upcoming coming small biotechs caught our attention and may turn out to be future stars
National Harbor – There were quite a few gems in the poster halls and oral presentations from up and coming small cap biotechs at the Society for Immunotherapy of Cancer (SITC) meeting this year.
Who were they and what did we learn from them?
In the latest part of our latest SITC coverage we highlight 13 presentations – 11 from small biotechs and 2 academic abstracts – that caught our attention, explain what’s intriguing about them and why they matter.
There’s not a single big Pharma included (unless as a reference point or given in combination) since the focus is mainly on up and coming companies with their novel approaches.
The list is quite selective and not at all random from a list of over 850 abstracts.
So what stood out and what was special about them?
Some of the selections are likely hidden sleepers that few will be familiar with… they also cover a wide range of approaches, targets, different modalities and even strategic intent.
Even if you were at the SITC 2019 meeting, increasingly there were more business meetings taking up valuable time than sessions attended, so this is a great way to catch all the highlights for your trip report 😉
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National Harbor, MD
With the abstract drop from the 2019 Society for the Immunotherapy of Cancer (SITC) meeting now available, what can we learn from some of the research slated for formal oral presentation this year?
Here in part one (posters will be reviewed tomorrow) we take a look at a mix of preclinical and early clinical studies that grabbed our initial interest from the oral presentations – they include the good, bad, and intriguing – to see exactly what can be learned from this year’s mix of abstracts?
The short answer is quite a lot.
Every year the what to watch out for preview is a popular one. This year there are some surprises in store as well as some particularly important findings that BSB readers may well be keen to find out more about ahead of the conference later this week in order to maximise their thinking and avoid the inevitable brain-fry and fatigue that sets in on Saturday afternoon…
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NKTR-214 Cover on Cancer Discovery
In the third part of our mini-series on cytokines, we get down and dirty with another pegylated IL-2 approach, this time from Nektar Therapeutics, including an interview with the PI, Dr Adi Diab from MD Anderson Cancer Centre and CSO, Dr Jonathan Zalevsky.
We’ve certainly had many full ranging discussions and chats with the good gentlemen; here we continue our journey to understand more about the science and underlying biology, as well as key biomarkers of response.
We can also be provocative too and put them on the spot regarding their critics and some of the pointed questions that get bandied about, which certainly makes for interesting reading. Are they justified?
What should we be looking for when analysing the data? You can find out for yourselves in the latest expert interview.
Other pertinent topics are also covered including where they’re headed and future data readouts to expect.
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In wave 3 of the immuno-oncology surge things have slowed down, partly due to a raft of combination trials yet to read out and partly because the reality has finally hit that tumour heterogeneity means there will be variable patient responses.
Just getting from room to room on time can be a real challenge with 40,000 other people present!
This complexity can come about in many forms… immunosuppression, alterations in gene functions, resistance and immune escape, to name a few.
If we want to help more people respond to these therapies then before we can rush headlong into another round of combination trials, we first have to go back to looking carefully at the underlying biology of the diseases and listen to what the patient’s tumours are telling us in order to fix things.
To accomplish this feat requires considerable time, energy, effort, and a lot of bioinformatics.
In this post we explore five key talks that highlight different aspects of biomarkers of response and mechanisms of resistance. From there, we may see additional validation and prospective testing to determine how best to segment people so that they have the greatest chance of responding to the therapy administered.
One thing that most people don’t have these days is time, which is how we can help you because here’s a handy short cut to finding out more about five complex and diverse areas on biomarkers or IO resistance quickly and easily…
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Continuing our in-depth oncology pathology interview with Dr David Rimm (Yale), we take a look at some of the new data his lab presented in Atlanta, where we are now with TMB as a biomarker, and what the future may hold for cancer immunotherapy biomarkers.
Early morning in Atlanta en route to the GWCC and AACR19
In an engaging discussion, Dr Rimm discussed many of the details behind PD-L1 and TMB in terms of what really matters when thinking about these tests and their practical applications. He also shared his candid thoughts on the lung cancer blood TMB data presented at AACR by Prof Solange Peters.
If you missed the first part of the interview with Dr David Rimm, a leading oncology pathologist at Yale, on the various challenges associated with PD-L1 as a biomarker on tumour and immune cells in triple negative breast cancer than you can catch up and read it here.
The second half of the interview with Dr Rimm focuses on TMB, with some more details on the challenges of reading PD-L1 on immune cells and why that is the case…
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Paths to success in cancer research
It’s time to pull together some notes, ideas, and clinical data on various biomarkers based on data available from clinical studies in oncology R&D and see how much progress we are making.
Are biomarkers a good path to success in cancer research or are they a gloomy red herring to the road less travelled?
Both answers can be equally true, but how do we tell the difference? Are there any clues that we can use ahead of time to avoid later disappointment?
There have been several early studies that we’ve been following lately with readouts available from numerous cancer conferences, both positive and negative.
Can we learn from the failures and successes of the past to better interpret outcomes from future trials?
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