After yesterday’s popular update on Ignyta where we posted our recent interview with the CEO, Dr Jonathan Lim prior to the 2Q conference call, a flood of questions have come in from eager beaver BSB readers.
Rather than add to an already lengthy article, this seemed a good opportunity to start afresh and do our latest Reader Q&A mailbag on a specific topic, namely the TRK/ROS1/ALK space.
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After a long lull on the targeted therapies front – outside of EGFR T790M in lung cancer – this year’s ASCO has plenty to be cheerful about with new data across multiple tumour types. We can’t cover them all here, but more will be discussed in the Daily Live Blogs starting on Saturday.
Which drugs are going to be in roaring back after a quiet period? Which ones will be having a more muted meeting?
For those of you who are working in the targeting therapy world, take heart, there is a future beyond cancer immunotherapy; it is not the universal panacea and will likely not cure every cancer, at least for now.
There’s still a market opportunity for targeted therapies in cancer, and as we mentioned in yesterday’s ASCO Preview, there is also potential for the combination of targeted therapies with immunotherapies, so long as the combined toxicity is manageable and doesn’t outweigh the benefits.
In this post we’re looking at a selection of targeted therapies in a variety of tumour types. There’s a lot to choose from at ASCO this year.
Here’s a few we think are worth highlighting upfront.
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Over the last decade we have seen some real progress with some subsets of lung cancer, particularly in EGFR mutated and ALK translocated tumours. Indeed, an incredible amount of translational work has emanated from just a few groups based in Boston, New York and Hong Kong.
Dr Jeff Engelman Source: MGH
At AACR earlier this year, Dr Jeffrey Engelman (MGH, Boston) gave a fantastic talk not just about heterogeneity, resistance mechanisms, but also on how lung cancer can transform. Included in his review was the role of biospies and how he sees those evolving.
I’ve been meaning to write up this important talk since April, but decided to wait until the key publications that were in press at the time were actually published – it was a longer wait than expected!
In general, it is our policy to write up published, rather than unpublished data, out of respect to researchers. It also makes it more useful to readers when the translational and clinical data is publicly available for those interested in reading the in-depth research articles. We also gathered commentary from other though leaders in the lung cancer space for some additional insights.
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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:
“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”
There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.
To maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.
When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!
I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research. Thank you for joining our conference coverage service, we really appreciate it.
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It’s a while since we discussed ALK+ lung cancer, but with new data coming out at ESMO last week, this is a good time to take stock and see what’s happening with the next generation inhibitors in a post crizotinib (Xalkori) world. These include ceritinib (Zykadia), alectinib and Ariad’s AP26113, which just received Breakthrough Therapy Designation from the FDA.
At ESMO two years ago in Milan, it was quite clear in a dedicated ALK session that these agents not only looked very promising, but were also likely to be fast tracked to market in patients with crizotinib resistance. All are more potent (based on the IC50) than crizotinib, while some target point mutations associated with crizotinib resistance and others have activity in patients with brain metastases, which is one of the common causes of progressive disease with crizotinib.
Today’s post is a long and meaty one – it not only covers data that was presented at the meeting, but also offers a glimpse into the changing ALK landscape.
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Boston – Preclinical data for PF-06463922 (Pfizer), a next generation ALK inhibitor, with potency for all known Crizotinib ALK resistant mutants and ability to cross the blood brain barrier was presented today at the 2013 International Conference on Molecular Targets and Cancer Therapeutics co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC).
In addition to being a competitor to other next-generation ALK inhibitors in development such as AP26113 (Ariad), LDK378 (Novartis) and alectinib (Roche/Chugai), PF-06463922 shows activity in both crizotinib-naive and crizotinib-resistant cells, so could end up being a replacement for crizotinib (Xalkori) front-line if clinical results confirm preclinical efficacy.
Some interesting early drugs in development were presented in a packed session this morning, across a wide variety of targets and tumour types. The four that stood out from the pack to me were:
1) MEDI4736 (anti-PD-L1)
2) GDC-0980 (dual PI3K/mTOR)
3) BKM120 (buparlisib) + GSK112 (trametinib) (PI3K + MEK)
4) alectinib (ALK)
It’s been a long 14+ hours here on the first day of ECCO in Amsterdam and I’m starting to flag
There’s a lot going on in lung cancer right now, which is pretty amazing when you consider only a couple of years ago we were still talking only chemotherapies and EGFR inhibitors.
Much of the new attention has been on the EML4-ALK translocation, the T790M mutation responsible for EGFR resistance as well as the possibility of improved survival with either MET or MEK inhibition. There are others, but these are the main ones that jump to mind.
Today, I want to focus on ALK+ lung cancer and what’s in store at ECCO at the weekend.