Yesterday Novartis announced the initial data from the JULIET trial in relapsed/refractory aggressive lymphomas such as diffuse large cell lymphomas (DLBCL) that were presented at the upcoming International Conference on Malignant Lymphoma (iCML) meeting in Lugano.
Here at BSB, we’ve been following CAR T cell therapy developments in earnest since 2012 when Penn and Novartis first announced their collaboration to develop what is now known as CTL019.
Five years on, we now have two such cell therapy products already filed with the Health Authorities and the JULIET trial will likely be the third indication submitted by the end of the year. This niche is now well established for regular readers and not something that has been a flash in the pan over a year or so.
There are a few interesting points of note on the CAR T cell front that are also worth exploring in conjunction with this news.
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Long time attendees at the annual meeting of the American Association for Cancer Research (AACR) know that there are usually interesting posters and sessions buried on the last day of the meeting.
This year was no exception, with a major symposium on “CAR T Cell Cancer Immunotherapy” chaired by Michael Jensen MD (pictured right).
BSB readers will recall we interviewed him at the 2016 BMT Tandem meeting in Honolulu (See post: Optimizing CD19 CAR T cell therapy). Excerpts from this interview also featured in Episode 14 – Cell Therapy Pioneers of the Novel Targets Podcast.
The CAR T symposium on the last day of AACR was one of my highlights of the meeting. The three speakers were:
- Michael Jensen, MD (Seattle Children’s) Engineering Next Generation CAR T cells using Synthetic Biology-Inspired Technologies
- Terry J. Fry, MD (National Cancer Institute) Defining and overcoming limitations of CD19 CAR immunotherapy in pediatric ALL
- Christine E. Brown, PhD (City of Hope) Progress and Challenge in CAR T Cell Therapy for Brain Tumors
Each of these presentations would merit a full blog post in their own right, but in this particular post we’re focusing on CAR T cell therapy targeting glioblastoma multiforme (GBM).
GBM is the most common primary malignant brain tumor, and one with a dismal prognosis – the 5-year survival rate is only around 5%, so there is also a high unmet medical need for new effective treatment options. This devastating disease has proven to be a miserable graveyard for Pharma over the last decade, with many agents unfortunately ending up in dog drug heaven.
After her AACR17 presentation, Dr Brown kindly spoke to BSB.
This post is part of our series of thouight leader interviews from AACR17. It also continues our ongoing posts on the adoptive cellular therapy landscape, and in particular, CAR modified T cells.
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It’s finally time…
US Capitol Building, DC
By popular request from BSB readers, we have a CAR T cell therapy preview of the main abstracts to watch out for, including talks and posters, and what emerging themes to expect are likely to be.
If you are registered on the AACR site and signed in, then clicking on any of the abstracts highlighted in this review will enable you to add any interesting ones you fancy to your conference itinerary.
There’s a surprising amount to cover this year, especially when we consider the incredible work that’s ongoing to address a number of suboptimal aspects in the construct developments. It’s continuing to progress at warp speed, so hold onto your hats and buckle down for our latest rock around the AACR clock.
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Hans Bishop, Juno
After a rocky 2016 for Juno with JCAR015 and the trial that imploded unexpectedly and badly, the CEO Hans Bishop quietly announced that announced that ROCKET has been abandoned:
“2016 was a year of progress and learning for Juno and the cancer immunotherapy field. We continue to experience encouraging signs of clinical benefit in our trial addressing NHL, but we also recognize the unfortunate and unexpected toxicity we saw in our trial addressing ALL with JCAR015. We have decided not to move forward with the ROCKET trial or JCAR015 at this time.”
A strange year of hubris attracting nemesis might be another way of describing the events for some observers.
We covered the Juno roller coaster and events in July and December 2016 for those who want to catch up on the full history of this unfortunate and ongoing debacle:
Where does the latest Juno news leave things and what can we expect going forward?
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One of the pioneers of CAR T cell therapy in children is Dr Stephan Grupp, who is Director of the Cancer Immunotherapy Program at The Children’s Hospital of Philadelphia (CHOP).
Dr Stephan Grupp ASH16
He led the way in developing ways of treating cytokine release (CRS) syndrome through the use of tocilizumab. At the recent American Society of Hematology annual meeting, Dr Grupp presented the results of the ELIANA study, the first global, multi-center clinical trial with CTL019 (Novartis) in pediatric acute lymphoblastic leukemia (p-ALL).
What was surprising to many at ASH was that despite the fact that CAR T cell therapy is one of the hottest topics in hematology (if not the hottest), many presentations were in small (tiny) meeting rooms, which many people could not get into. Several overflow rooms were rapidly opened up, but still people were left out. Someone clearly did not get the memo!
If you didn’t make into the meeting room at ASH to hear Dr Grupp, he kindly spoke to BSB about the data he presented and also shared his perspective of what the future may hold for CAR T cell therapy in pediatric ALL.
There’s also additional commentary on some of the other key CAR T cell presentations that caught our attention at ASH.
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Some cancer conferences attract more questions and queries than others.
Old Town San Diego
Interestingly, ASH is always a popular meeting for attendees and readers alike, so it is good to see another batch of critical questions come in so soon after the last one. It’s a while since we did two BSB reader Q&A mailbags from a single meeting!
Not surprisingly, there were also a bunch of questions on CAR T cell therapies, which continue to dominate readers minds, as well as related issues. Here, we answer the most pressing questions that have come in over the last week.
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After regularly reporting here at BSB on several readouts in terms of antibodies and CARs since ASH last year, it’s reasonable to conclude now that there has been growing interest in BCMA–APRIL as a target in multiple myeloma (MM). The CAR T cell therapies have generally focused on BCMA or BCMA-TACI as a target, while antibody approaches such as Aduro’s, BION–1301, target APRIL.
T cells attacking a cancer cell
These new therapies have all been either preclinical in nature or preliminary phase 1 studies in a very limited number of patients, meaning that the best we can characterise them is that old reliable chestnut, ‘promising but early’… to do otherwise would be rather extravagant and hopeful at best.
Given the data from several CAR T cell therapy studies were being presented at two meetings on two separate continents only a few days apart, it makes sense to review them as a whole.
It’s therefore time for a detailed update, including a review of the differences in the key studies, a look at where we are now, as well as tips on what to look for going forward.
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This is an important and necessary follow-up to the ongoing Juno JCAR015 story in July after three patients had died due to complications associated with cerebral oedema. At that time, the company attributed the deaths to the inclusion of fludarabine in the lymphodepletion given prior to CAR T cell therapy infusion, leading to severe neurotoxicity, and clinical hold was lifted by FDA after the protocol was subsequently amended.
This morning came the dramatic announcement that following the protocol amendment, Juno has voluntarily placed the ROCKET trial on clinical hold again following another two deaths from cerebral oedema.
What gives and what are the consequences here?
We take a joint look at some of the issues that arise from this situation in terms of the CAR T cell therapy market and also pen thoughts from the analyst call this morning.
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It was only five years ago that the number of abstracts on CAR T cell therapies at the American Society of Hematology (ASH) ran to a dozen or less. Fast forward to 2016 and we now have tens of them, almost too many to count, let along review quickly and easily.
A scene from ASH 2015…
To give you an idea of the staggering speed of progress, in 2010 it took me less than half an hour to search and read all the CAR T cell abstracts, now it takes nearly a whole day to peruse and review them carefully.
We can’t resist a challenge…
As usual, we will write in more depth from the meeting as the data emerges in real time since many of the abstracts are often placeholders with updated information provided at the conference itself.
For now, here we provide an in-depth preview of the CAR T cell landscape in terms of the players, the products, new scientific research, biomarkers, emerging trends and more in a handy What to Watch For (W2W4) guide on key areas to expect at ASH to enable better enjoyment and awareness as the data rolls out next month.
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Late this afternoon, Juno Therapeutics ($JUNO) announced (link to press release) that the FDA had put a clinical hold on enrollment into a phase 2 trial of their JCAR015 construct in relapsed refractory acute lymphoblastic leukaemia (ALL) in adults in the ROCKET Trial: NCT02535364.
The decision by the FDA was as a result of three recent patient deaths reported to be due to neurotoxicity. In after-hours trading the stock dropped 30% from a market close of $40.82, reaching an after hours low at time of writing of $26.66 at 4.43pm ET.
In this post we look at what happened, the possible reasons behind it, and what it may mean for other CAR T companies. A leading CAR-T cell expert also provided BSB with some commentary after the news broke.
Good News: Post now updated following FDA lifting hold on ROCKET trial.
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