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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Chronic Lymphocytic Leukemia (CLL) was one of the hot topics at this year’s annual meeting of the American Society of Hematology (ASH), and a new CLL drug that caught my attention was the second-generation Bruton’s Tyrosine Kinase (BTK) inhibitor ONO-4059 from Ono Pharmaceuticals.
Professor Gilles Salles (Lyon, France) presented promising efficacy data from a phase 1 study of ONO-4059 in relapsed/refractory CLL and high risk CLL (#676).
Unfortunately after his presentation, Prof Salles declined my request for a quick interview citing a prior commitment with a large pharma company and subsequently failed to turn up for an agreed interview the next day. Talking about ONO-4059, at least with the media, did not appear to be a priority!
However, as a potential competitor to other BTK inhibitors in development such as ibrutinib (Pharmacyclics/JNJ) and CC-292 (Celgene/Avila) it’s worthy of a mention in the conference coverage and a quick post about the data presented.
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The chronic lymphocytic leukemia (CLL) landscape has been one of the most dynamic and exciting over the last 12 months, with many new therapies emerging against different targets from CD20 to BCR signaling, Bcl2 to the PI3K pathway. Other new targets may also soon emerge.
The annual meeting of the American Society of Hematology (ASH) in New Orleans sets the scene for the rollout of more mature data and affords an early evaluation of where the various companies competing in this space may shake out. Given that we are moving beyond traditional chemoimmunotherapy to evaluate several newer classes of therapy including B cell receptor (BCR) and PI3K signaling, anti-CD20 antibodies, anti-CD19 chimeric antigen receptor T cell technology (CART) it looks to be shaking out to an exciting conference.
Companies mentioned: Roche/Genentech, Gilead, Pharmacyclics, Abbott, Celgene, Infinity, Incyte, ONO, Amgen, TG Therapeutics, Novartis
Products discussed: rituximab, bendamustine, obinutuzumab, idelalisib, ibrutinib, ABT-199, CC-292, GS-9973, IPI-145, ONO-4059, INCB40093, AMG 319, TGR-1202, CTL-019