Tropomyosin receptor kinase (TRK) inhibitors are not a name that rolls off the tongue easily and yet this niche is attracting a lot of interest from observers curious to learn more about a highly targeted approach to rare oncogenes such as TRK, ROS1 and ALK that occur in several different tumour types.
Much of the focus has been on the more commonly expressed ALK-positive lung cancers with crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and others. Crizotinib also targets ROS1 and is approved by the FDA in metastatic NSCLC whose tumors are ROS1-positive.
As the next part of the development in this sphere, TRK and ROS1 mutations are now in the spotlight. Indeed, we have been reporting on the data since 2014, which has been encouraging thus far, particularly from two companies, namely Ignyta and Loxo Oncology. These two agents differ in that entrectinib targets TRK/ROS1/ALK whereas larotrectinib is a specific pan TRK inhibitor.
There was a new raft of data at the recent AACR annual meeting and more data is expected at the forthcoming ASCO conference.
Here, we take a look under the hood through the lens of one of the small biotechs in this space via a candid interview with Ignyta CEO, Dr Jonathan Lim.
Dr Jonathan Lim, CEO Ignyta
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At the European Cancer Conference (ECC 2015) held in Vienna recently, a number of promising targets emerged along with new drugs in development in several different tumour types. Not all of them were from big Pharma – some were from up and coming young biotechs that will be worth watching out for.
In this first part of our ‘New Drugs on the Horizon’ mini series, we chose four interesting and largely positive studies to highlight and discuss in-depth.
In the past, there were many negative trials to pick over and ponder why they didn’t quite pan out. After all, it’s relatively easy to be an armchair critic and hindsight is a wonderful thing.
Picking only four from the many promising choices of trials presented this year available turned out to be quite hard given there were many that caught our attention – a bit like choosing only one of four out of the many schnaps to sample locally!
Today’s review looks at four very different drugs and approaches in early development from Pfizer, Stemcentrx and Ignyta – they include encouraging early data on both small molecule tyrosine kinase inhibitors (TKIs), as well as antibody drug conjugates (ADCs).
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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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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)