San Francisco: In the final post of the week, it’s time to focus on some of the interesting concepts and early ideas being explored in GI tumours such as pancreatic and colorectal carcinomas.
Gems from the Poster Hall or what Dog Drug Heaven really looks like?
Despite the image implied by the used poster bins (right), there were actually several encouraging signs from emerging IO approaches as well as some surprising results that lead to some compounds – or at least some indications – going off to dog drug heaven.
There were also some salutory lessons to be learned in terms of understanding biomarkers and useful these can be.
After years of incremental improvements with targeted therapies, it’s time to look at whether some immunotherapy combinations can make an impact in what is known as cold tumours.
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San Francisco: ASCO Gastrointestinal symposium 2017 – Update on metastatic colorectal cancer
It might surprise quite a few people that colorectal cancer (CRC) is the third most commonly diagnosed cancer globally, especially in the western hemisphere where hereditary, dietary and lifestyle factors can be important.
The bedrock of therapeutic approaches in this disease have largely centred around chemotherapy (FOLFOX or FOLFIRI) along with targeted therapies against EGFR (cetuximab, panitumumab) or VEGF (bevacizumab, ziv-aflibercept, regorafenib etc).
In our second report from #GI17, we take a look at some of the emerging monotherapy and combination approaches that are showing early signs of moving the needle in advanced CRC, an area that has been relatively dormant of late. This is partly because it’s a cold tumour and with the focus on cancer immunotherapies, it’s not the first tumour type that companies will necessarily rush to evaluate.
Things are changing though, even in colorectal cancer so it’s time to look at some key studies that may teach us more about this disease.
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Challenges and Opportunities in the evolving 1L NSCLC Landscape
Rolling English Landscape in Devon
Following a series of events – from BMS’s failure with nivolumab monotherapy… to Merck’s sudden announcement to file their combination of pembrolizumab plus chemotherapy… to AstraZeneca’s delay of the MYSTIC trial exploring durvalumab plus tremelimumab this week, there’s never a dull moment in lung cancer!
So can we expect some more surprises in store in 1L NSCLC?
I say yes we can!
The big questions are what are they and what impact will they have?
2017 is ironically, the year of the Rooster – so who’s going to crow loudly at dawn and who is going to get strangled in the process?
In the world of cancer research it is unlikely that everything wins or is successful, so figuring out the early signs and hints is an important part of the process.
One thing I learned early in this business is that it pays for companies to be humble, flexible and open minded rather than arrogant and dogmatic in their thinking… otherwise you can easily be blindsided.
There were a few examples of that in oncology R&D last year, a repeat could very well follow in 2017 for the unwary.
Here we look at 1L NSCLC in the context of multiple phase 3 trials that are slated to read out… from AstraZeneca, BMS, Merck and Genentech.
If you want to know what the potential impact of these events are on the landscape, including what we can expect from MYSTIC, CheckMate-227 and several others, then this is the post for you because some surprises are likely in store.
We cut through the chase to explain the what and the why in clear simple language.
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The 2016 Congress of the European Society for Medical Oncology (ESMO) is fast approaching. It takes place next month from October 7th to 11th and we will be on site covering the meeting for Biotech Strategy Blog. We’re looking forward to a great meeting!
If you are sitting on the fence as to whether you should go to Copenhagen, then hopefully our series of Previews will help you decide.
Be warned that accommodation is in already in short supply and ESMO are now putting people up across the Oresund bridge in Malmo, Sweden.
The Congress App has a lot of useful information and is well worth downloading, if you haven’t done so already.
Last week many of the late breaking abstract (LBA) titles were announced, although there are still some placeholders. While we won’t know the actual late-breaking data until the meeting, the LBA titles offer insights into what will be presented in Copenhagen.
In the second in our ESMO 2016 Preview series, we’re highlighting the lung cancer late breakers that we’re looking forward to hearing, providing some background on why they may be of interest, and a look at how some of subset landscapes may be a-changing in the future.
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Tesaro’s niraparib is a highly selective poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that can induce synthetic lethality in tumor cells with homologous recombination DNA repair deficiencies (HRD), including germline BRCA-mutated tumours. It received a lot of attention yesterday following the company’s announcement that the phase 3 trial successfully met its primary endpoint. The trial was expected to readout this month, so it was bang on schedule.
Braving the scrum in the ASCO 2016 poster hall
The results generated a lot of discussion and also a bunch (half a dozen!) of questions from readers, since there was a lot noise around the top-line data in the press release, but very little real analysis or context.
I was planning on rolling out the draft posts we have been working on Gems from the Poster Halls, which included one focused on ovarian cancer. It therefore makes sense to combine the poster analysis with a reader Q&A on ovarian cancer, including a detailed look at Tesaro’s niraparib as there are some important subtleties that many have missed.
Inevitably this ended up as a rather meaty analysis rather than the quick review I originally intended!
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One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.
Prof George Coukos AACR 2016
Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.
Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.
The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis (Link).
If you missed it, you can still listen to highlights in Episode 7 of the Novel Targets Podcast (Link).
After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.
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After exploring the science behind chemotherapy improving T cell trafficking into the tumour yesterday – which is one of the key rate limiting issues that need to be addressed with immunotherapies such as checkpoint blockade – some obvious follow-up questions comes to mind:
- Does the compelling data in mice translate to humans?
- Can chemotherapy turn a cold tumour into a hot one?
- Will patients have improved outcomes as a result – or not?
It’s easy to dismiss traditional therapies in favour of appealing new developments, but what happens when we combine them? Do we get additive effects, synergies or a negative impact?
As part of our ongoing AACR coverage, we explored this conundrum in the context of new data readouts, as well as the broader competitive landscape.
What we found was really interesting!
BMS, Merck and Genentech/Roche all have trials ongoing in the metastatic colorectal cancer space, with very different approaches being taken. Does it matter? Which one’s driving the bus? We summarise these trials and offer some strategic insights on this niche.
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New developments in renal cell carcinoma
Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).
There were two important announcments on Monday this week relating to renal carcinoma.
Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR). The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:
- Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
- Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
- Exelixis to complete US and EU regulatory filings in early 2016
Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.
There are some interesting points that fall out of these releases. To learn more, subscribers can log-in below or you can purchase a subscription in the box below.
We hope that everyone had a relaxing holiday break and now it’s time to get back to work. Tomorrow I will review some more of my thoughts in the immuno-oncology space, since that area had a tremendous amount of progress in San Diego with lots of new ideas to process and summarise.
In the meantime, a few people have written in and asked about what was happening with overcoming resistance in various tumour types, was there anything new to say in that space that was in addition to the the detailed previews we covered before the conference?
Actually, there was a quite a few posters and presentations that caught my eye, so I thought this would be a good idea to review them here:
Lung Cancer: HER2, VEGF, T790M, EGFR, erlotinib, gefitinib, trastuzumab, bevacizumab, CO-1686, AZD9291
Prostate Cancer: mTOR, PI3K, Androgen Receptor, enzalutamide, abiraterone, CC214–2, ARN–509, BET Bromodomian inhibition, ODM–201, GDC–0980, GDC-0068, PF–04691502, BKM120, BEZ235
In the second part of our mini-series on immuno-oncology, I thought it would be a nice idea to share a recent interview conducted with one of Roche/Genentech’s leading researchers in this field. I was particularly interested in their approach because while BMS and Merck have clearly focused on anti-PD-1, Roche and Genentech have effectively zigged with their development of an anti-PD-L1 inhibitor. Does this matter?
Here, we explore the general background to this approach and, in particular, where the company are going with their anti-PD-L1 inhibitor, MPDL3280A.
anti-PD-L1, anti-PD-1, anti-CTLA-4, checkpoint point inhibitors, T cells, biomarkers.
MPDL3280A, nivolumab, MK-3475, ipilimumab (Yervoy), lirilumab, BMS-986016 (anti-LAG3), bevacizumab (Avastin), erlotinib (Tarceva), vemurafenib (Zelboraf), cobimetinib.
If you are interested in more background on how the PD-1 and PD-L1 inhibitors work, you can check out the mechanism of action (MOA) in our video preview from ASCO last year, which explains this in fairly simple terms.
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