National Harbor, MD
Despite remarkable results with cancer immunotherapy to date, we do need to keep out feet on the ground and remember that response rates are relatively low to modest (10–30%) and the majority of patients do not respond or see a benefit with these approaches.
As we start moving beyond checkpoint monotherapy, the realisation has fast hit many researchers and companies that we really don’t know as much about the tumour microenvironment (TME) as we would like.
No doubt we will learn a lot more about it from the combinatory approaches, but be aware that this also means higher risk associated with such developments – we will likely see a lot of failures – and hopefully, some successes too.
This is where the little biotech companies have an opportunity to shine… they may have some intriguing IO compounds in development but not an anti-PD1/L1 backbone, meaning they can collaborate with a big pharma company to explore novel combinations in small phase 1/2 trials to determine what works or not. This is much lower risk (and R&D costs) for both parties and we get to see more quickly where things shake out.
At the annual Society for Immunotherapy of Cancer (SITC) meeting last week, there was a whole day devoted to New Immunotherapy Drug Development.
Some of these agents look worthy of watching out for and following their progress. A variety of data in different targets and MOA were presented from big and small companies alike. We selected a few of the promising ones for further review and discussion.
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We’ve had a couple of requests come in for a revival of the old conference series… ‘Gems from the poster halls’ because quite a few folks are interested in the up and coming data from small to medium biotechs.
A bunch of my Post Doc chums in this field were at the San Antonio Breast Cancer Symposium (SABCS) meeting and gleefully highlighted mobbed posters or areas where they thought the data looked potentially interesting.
From these, we selected a few for review in today’s look at the nuggets that can be gleaned from cool and intriguing trials or preclinical research that may influence future trials.
Companies covered in this article include Seattle Genetics, Jounce, Immunomedics, Syndax and MedImmune.
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With the recent approvals of nivolumab (Opdivo) and pembrolizumab (Keytruda) in advanced lung cancer as well as new checkpoint inhibitor data presented on atezolizumab at the European Cancer Conference in Vienna, there are several new lung cancer immunotherapy controversies to consider such as…
- How do we choose between docetaxel chemotherapy versus anti-PD1/PD-L1 immunotherapy?
- Which checkpoint should we choose?
- Is the PD-L1 biomarker useful and important?
- Do the company assays differ?
Dr Jack West
Dr Jack West (Seattle) got the ball rolling on some of these issues earlier this month, generating quite a spirited and useful debate on Twitter, demonstrating that clinical decisions in this area are not as cut and dried as many might think.
In addition, we spoke to a number of lung cancer experts in Vienna for their perspectives on the data, the biomarkers, treatment paradigms and other critical issues.
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With the launch of Episode 4 of the Novel Targets podcast today, I wanted to provide some more detailed background and a roadmap for this part of the journey for subscribers. There’s tremendous wealth of data now building up in several areas related to cancer immunotherapy and both interviewees, Drs Oliver Sartor (Tulane) and James Gulley (NCI), touched on many of them.
Thanks to Tom Gajewski’s exciting work, we can broadly think about different tumour types as inflamed (immunogenic) versus non-inflamed (non-immunogenic), which is a helpful starting point. Not all tumours thought to be responsive to immunotherapy will actually respond though, so we still have much work to do on the 70–80% of patients with solid tumours that don’t respond to these therapies.
Anyone who is interested can listen to the latest Novel Targets podcast.
The latest episode explores non-immunogenic tumours, using prostate cancer as an example. In the last third of the show, we do indeed talk about a promising new target that may have relevance not just to prostate cancer, but other tumour types too.
Listen to Episode 4 (open access thanks to our sponsors, Genentech)
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Picture Credit: @gene_antibody
For much of the last two years, one of the hottest topics around has been T cell manipulation, which can happen in many different forms.
This is just one area that we have covered extensively in the immuno-oncology space from Chimeric Antigen Receptor (CAR) T cell therapies to checkpoint inhibitors, as well as various antibodies, including the first bispecific T-cell engager (BiTE) to CD19 that recently approved by the FDA called blinatumomab (Blincyto) from Amgen.
Not all cancer patients respond to all these approaches though.
Why is that and what approaches or novel targets can we explore next to address this vexing issue?
At the SITC and SABCS meetings, I saw some really interesting and unusual presentations, together with some recent publications on topic, that really piqued my interest in this challenge. They are early signs of the new directions some of the research in this field could go. Overcoming resistance and understanding different aspects of immune escape will likely be very instructive in developing the next generation of combination studies that could make a positive impact on patients.
Today’s post touches on some of these exciting developments and includes an in-depth interview with Dr Ira Mellman, the scientist behind Genentech’s immunology research program at gRED.
Interested readers can log-in to read more about the exciting new developments that are happening with different types of antibodies in the immuno-oncology space.
With all the heightened interest in checkpoint inhibitors of late, I wanted to continue my series on what did we learn from the updated data at ESMO that was different from ASCO? Last week we discussed gastric and bladder cancers, this week it’s the turn of lung cancer, or more specifically, non-small cell lung cancer (NSCLC).
By chance, some interesting announcements have also happened since ESMO with the third quarter earnings calls going on from the main players in this space, which also add colour to the developments in this niche. BMS, for example, announced that they expect their rolling NDA for Opdivo in lung cancer to be completed before the year end and will be presenting the CHECKMATE 063 data this week, while Merck announced their Breakthrough therapy designation for Keytruda in lung cancer this morning.
All in all, this makes the lung cancer space a lot more exciting than it was at ASCO, where the response to the data was fairly muted.
To learn more about the updated ESMO data and the impact of the recent announcements in lung cancer, you can log-in to read our insights.