It’s that time of the month where the BSB readers get their chance to put us on the hot spot!
Here, we take a look at reader questions that have been submitted and argue the toss – is there evidence preclinically or clinically that is useful or instructive?
We can’t promise to answer every question, sometimes there simply isn’t any data to help either way.
This week, the topic is CAR T cell therapies, a subject that seems to be very high on many people’s minds and many of you had similar questions, so here goes…
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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).
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One of the things I most enjoy in cancer research is hearing wonderful patient stories from oncologists who are at the coal face of clinical trials. They get to deal with death and dying every day and like those in Pharma R&D, also live for the successes, the drugs that make it through pipeline despite great odds against them and make a meaningful impact on the daily lives of ordinary people.
We’ve all heard topline data presented at medical conferences around the world, but what the summary data can’t tell you is how a drug can impact people in ways that are clinically meaningful yet are more obtuse to capture in the aggregate. This is why case studies at CME sessions are increasingly popular, because they add value and context to common issues in a way that a Kaplan-Meier curve can never do.
With the flurry of recent US and EU approvals for obinutuzumab (Gazyva), ibrutinib (Imbruvica) and the newest kid on the block, idelalisib (Zydelig), in CLL and indolent lymphomas, I wanted to take a look at these drugs from a different perspective.
A reader wrote in asking which of these new agents would emerge the winner and why?
Today’s post therefore offers some thoughts on the emerging CLL landscape now that we are shifting from new product development to the marketplace.
Drugs mentioned: Gazyva, Imbruvica, Zydelig, ABT–199/GDC–0199, Arzerra, IPI–145, CTL–019
Companies: Roche/Genentech, J&J/Pharmacyclics, Gilead, GSK, Infinity, Novartis
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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
Immuno-oncology is fast becoming one of the hottest topics in cancer research following the approval of the anti-CTLA4 checkpoint antibody, ipilimumab, in advanced melanoma, as well as emerging solid data from anti-PD-1 and PD-L1 antibodies in melanoma, lung and renal cancer at ASCO in June.
The big question on many people’s minds though, is what other checkpoint inhibitors are out there and can they safely be used either as single agents or in combination with the above agents, or even with existing standard of care combinations (chemotherapy and targeted therapies)?
I have long argued that what will really make a difference in this space is combinations and the ability of sponsors to successfully evaluate novel-novel agents in clinical trials. After all, BMS have a huge advantage with ipilimumab and the ability to combine it with their PD-1 or other immunotherapeutics, since their rivals will be greatly hampered by the $120K per person price tag for the commercial drug required as part of clinical trial costs.
This means most companies in this space are looking at other options in the search for better outcomes.
At the AACR-NCI-EORTC Molecular Targets conference in Boston this week, the last day was devoted to two sessions in immune-oncology and one of the plenary sessions included Dr Susan Topalian discussing an update on nivolumab and anti-PD-1/L1 therapies post ASCO. There was also ample opportunity to discuss immunotherapy with the many attendees in the busy poster sessions.
The first immunotherapy session on Weds morning particularly caught my attention and it seems a good opportunity to summarize some of the key observations emerging in this field. Here are my detailed notes from the session, which raise a lot of fascinating questions from the presenters about this field and – more importantly – where it’s going: