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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SITC 2019 Preview: After looking at exciting new developments in targeted therapies last week, it’s now time to switch horses and kick off our annual coverage of the Society for Immunotherapy of Cancer (SITC) meeting, which takes place in a few days time at National Harbor in Maryland.
National Harbor, MD
In the SITC 2019 Presidential Session this coming Saturday, one of the presentations we are eagerly looking forward to is by Dr Vyara Matson, a Post Doc in the lab of Dr Tom Gajewski at the University of Chicago.
Dr Matson will be presenting on “Patient-derived microbiota germ-free mouse model for identifying mechanisms of checkpoint blockade efficacy modulation.”
In our latest expert interview, we spoke to Dr Gajewski about the strategic concepts underpinning his work in the microbiome niche, where he has got to presently and where he plans to go next. It makes for fascinating reading, especially when you realise that as scientists, they are sceptical themselves and yet curious to discover the answers through carefully thought out experiments that could impact future patient care for those people receiving immunotherapy for the treatment of their particular cancer.
One major take home for us in following the cancer immunotherapy niche is that there could well be different mechanisms at play for primary and secondary resistance – where does the microbiome fit in with this, and can it be manipulated to create a more positive benefit? Is the effect a real one or a spurious correlation? These kind of questions, along with a host of others, are some of the key topics discussed in the expert interview.
If you have plans to be at #SITC2019 do let us know, as we always look forward to saying “hello” to BSB readers.
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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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One key emerging area of growth (and importance) in cancer research is the validation, and hopefully clinical use, of more convenient and less invasive biomarker tests based on body fluids rather than tumour biopsies aka ‘liquid biopsies’.
With a glut of recent data now available from several trials, some of which might be considered controversial, and more to come in the next raft of cancer conferences, it seemed a good opportunity to take stock and see where we are, what we have learned, and importantly, where we are heading in this fledgling field.
In the BSB hot seat today we have our latest thought leader interview, where we discuss these issues and gain their perspectives on the latest round of data with blood TMB and whether it is turning out to be clinically useful or not…
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One of the ongoing challenges with cancer immunotherapy is monitoring response to treatment.
Even if you are one of the minority of people who do respond to cancer immunotherapy, many responders go on to develop acquired resistance or experience immune escape resulting in a loss of response to therapy, which means we need to be able to detect what is happening in the immune system of a cancer patient in order then identify the next treatment option.
Dr Whiteside in the poster hall at #AACR18
Could the proteins and nucleic acids carried by virus sized microvesicles called exosomes – present in their billions in blood plasma – provide insights into biomarkers of response to therapy and what is happening in the tumour?
Some people think they can, while others remain skeptical.
We think it’s cool area of research, worthy of consideration and following as we continue to explore various biopsy and blood/plasma approaches.
One person at the forefront of exosome research is Dr Theresa Whiteside from the University of Pittsburgh, where she’s a Professor of Pathology, Immunology and Otolaryngology.
At the recent 2018 annual meeting at AACR, she kindly spoke about her innovative work over the past year in what is now an exploding field of research…
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Chicago Loop Train
In this latest ASCO 2018 Preview, we take a look at tissue and blood based biomarkers to see what we can learn and whether they look useful or not for predicting which patients should receive a therapy or not.
There’s quite a lot we can learn from the latest data from the initial abstracts ahead of the meeting in order to be better prepared about what to expect in Chicago.
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