We’ve been hearing and writing about a substantial amount of news and information on various immuno-oncology developments over the last year, especially in metastatic melanoma and lung cancer, but despite renal cell cancer (RCC) being a proven immune-sensitive disease with known PD-L1 expression, it seems to be the poor cousin to the other two tumour types given the lag in data and relative media attention.
There’s actually quite a lot going on in this disease though, from biomarker work to phase I to III trials that are either ongoing or just started accruing.
We should be hearing much more about the role of anti-PD–1 and PD-L1 antibodies in RCC over the next couple of years, including data from some large randomised controlled trials, but what’s the current state of play?
With that in mind, I was deligted to catch up with David McDermott’s (DFCI) in-depth presentation at ASCO GU in San Francisco over the weekend. It’s always unfortunate when an interesting talk is left for the final presentation on the last day of a conference, as only a few diehards will be there to catch it! It was a well thought out discussion though and he covered a lot of interesting ground in this space.
ipilimumab, nivolumab, MK–3475, MPDL3280A, LAG–3, TIM–3, PD-L2, IL–2, sunitinib, everolimus, bevacizumab
BMS, Roche/Genentech, Merck, GSK, Novartis, Pfizer
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This week the Cancer Conference Coverage moves to the joint IASLC-AACR symposium on the Molecular Origins of Lung Cancer in San Diego. Having attended previous events (this is the third one they’ve hosted) and rather enjoyed them, this year I’m following it remotely.
What’s particularly nice about this type of specialist event is that they are especially useful for chatting informally with attendees and being able to ask a lot of questions that simply wouldn’t be feasible at larger meetings due to time and other constraints.
This review covers my thoughts on two immunotherapies, namely Merck’s anti-PD-1, which was previously presented at the World Lung Conference, plus a completely novel and very different approach that looks really quite exciting.
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As cancer becomes increasing complex with adaptive responses to therapeutic intervention, so our knowledge and strategies for overcoming it must also adapt and improve. Immunotherapy – in several forms – is probably the hottest topic on the landscape at the moment with both checkpoint inhibitors and chimeric antigen receptor technology (CART) vying for air time and attention but where are these approaches going and how can we harness the immune system more effectively?
One of the things I like most about AACR meetings is that there are nearly always some strategic gems emerging from the scientist-physician thought leaders if only you stop to think about how the field can rapidly change by looking at the early patterns that are emerging.
Here’s the first part of a synopsis of what I learned at the recent Molecular Targets meeting in Boston, some of these findings may well have a major impact on cancer research over the next few years…
Check point immunotherapy is probably on everyone’s hot topic list in oncology at the moment and rightly so.
One of the key sessions I’m looking forward to at ECCO is the Saturday Lung Cancer Symposium on new therapeutic targets. It includes not only a presentation on PD-1 and PD-L1 Immune checkpoint antibodies, but also overviews of progress in several other pathways, namely PI3K-AKT-mTOR, RAS-RAF-MEK and ALK+/Hsp inhibitors. This should be an excellent session that allows a broad overview of many of the key areas of research in the disease.
Aside from a late breaker on the two-year ipilimumab data in metastatic melanoma, the check point abstracts I managed to find in the #ECC2013 program appear to be all posters. Here are my quick notes ahead of the presentations for Premium Content subscribers:
For many years, scientists have tried – and failed – to develop techniques to activate the body’s immune system against cancer. The majority of these immunotherapy approaches, especially vaccines, simply didn’t have enough potency, or were based on a weak target that had little impact on advanced disease. The rationale for vaccines in cancer prevention is much stronger, as we have seen with the HPV vaccines, Gardasil and Cervarix, for example. When given to patients with advanced disease, the large tumour burden is usually too much for them to overcome and the cancer wins.
Although the immunotherapy field in oncology has been largely a graveyard with millions of dollars wasted and lost, there have been some notable successes. US approvals include rituximab (and other similar CD20 targeted antibodies) in B-cell malignancies, the IMiDs (thalidomide, lenalidomide, pomalidomide) in multiple myeloma, and ipilimumab, a human cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody in metastatic melanoma.
There are several interesting challenges with immunotherapies that must be overcome before successful therapeutics can be developed – Subscribers to Premium Content can login to read more below:
In her annual preview video of what’s hot at ASCO 2013, Sally Church (@Maverickny) discusses several therapeutic areas with new data at the meeting including:
- Immunotherapy (PD-1, PD-L1, CTLA-4)
- CLL (GA-101, idelalisib, IPI-145)
- Breast Cancer (palbociclib, PF-05280014)
- Lung Cancer (LDK-378, AP26113)
- Pancreatic Cancer (Abraxane, TH-302)
This video was originally published on Pharma Strategy Blog and includes an edited mechanism of action (MOA) for PD-L1 (courtesy of Roche/Genentech). Several people have since remarked it’s the first time they fully understood what “upregulation” meant.
If you missed the video, it’s well worth watching again in the run up to ASCO 2014.