What questions are BSB readers sending in to us this month?
I wanted to take a moment out of AACR Previews and catch up on some recent news that is intriguing or perplexing subscribers. All questions are anonymous and in many cases, the same questions were actually sent in by multiple people, a testament to what’s top of mind in oncology lately.
Today, we cover a Q&A on a variety of topics on Kite Pharma (the Genentech collaboration and their TCR in solid tumours), a discussion about EGVRvIII in glioblastoma, and Gilead’s woes with idelalisib and an IO pipeline.
So let’s get started – subscribers can sign-in or you can sign up via the blue box below:
The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.
While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front? Has hope been abandoned there or will we see a renaissance occur? It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon. Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.
Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?
Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?
Dr Carl June, U Penn
What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.
To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).
To learn more about Dr June’s perspective, subscribers can log in below or you can sign up in the box.
A couple of years ago we had a lot of fun here on BSB following the progress of ibrutinib (Imbruvica), obinutuzumab (Gazyva), and idelalisib (Zydelig) in CLL and indolent NHL. It seemed back then that the stunning trio were the hot topics for some time at ASCO and ASH meetings. Exciting times! All three target different entities (BTK, anti-CD20 and PI3K-delta) and made it past the tape to market, with Gazyva leading, Imbruvica a close second and Zydelig a slightly more distant third. I was reminded of the race again over the last week or so as the 4Q earnings were announced, with Pharmacyclics reporting almost $500M for Imbruvica last year and estimating sales to hit $1B in 2015. In contrast, Zydelig revenues for 2014 were $23M, reflective of their much later market entry in the US.
Still, that was a pretty impressive set of drugs all in development at the same time.
Two other agents we also reported on regularly were Infinity’s IPI-145, a PI3K delta-gamma inhibitor, and ABT-199/GDC-0199 (now known as venetoclax). I haven’t heard much about the former of late, but after a few missteps, the next big question to consider is whether venetoclax is coming back strongly or destined for dog drug heaven?
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During the recent American Society of Hematology meeting, much of the focus in immuno-oncology was squarely on the pediatric and adult data using the chimerica antigen receptor T cell product being developed by Novartis, CTL019, in acute lymphoblastic leukemia (ALL) from Children’s Hospital of Philadelphia (CHOP, not to be confused with the chemotherapy regimen!) and U Penn, respectively. We wrote about that data earlier this year.
There are, hovever, other interesting CAR T cell therapies in clinical development, including those from Juno (based on the MSK and Fred Hutchinson partnership), Bluebird in partnership with Celgene and one that actually had data at ASH, which didn’t receive much attention from the NCI and Kite Pharma. This therapy was evaluated in a trial of non Hodgkin’s Lymphoma (NHL) patients.
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Originally, I was thinking of doing an in-depth review of lymphomas i.e. non-Hodgkin’s lymphoma (NHL), which involve 85% of lymphomas and Hodgkin’s lymphoma (HL), which take up the remaining 15%. This topic, however, has been largely done to death already.
There are are some very useful sources of carefully curated content that I enjoy following every year and in this post I’m going to direct you to some of those and highlight where I think the critical topics are in lymphomas.
Companies mentioned: Roche, GSK, AbbVie, Pharmacyclics, Gilead, Infinity, Seattle Genetics
Drugs mentioned: Rituxan, Arzerra, Gazyva, ABT-199, ibrutinib, idelalisib, IPI-145, Adcetris