Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘CTL019’

After some relatively quiet summer months, we have been deluged with questions and requests this month for commentary on some hot topics of late. This seems like a good time to take stock and reflect on some of most frequent ones sent in.

west-acton-tubeThe original Journal Club post slated for today will appear next week instead.

Here, we address numerous queries on the following five topics readers are interested in:

  • APHINITY trial in HER2+ adjuvant breast cancer
  • Array’s BRAF plus MEK data in metastatic melanoma
  • Kite’s interim ZUMA–1 phase 2 announcement
  • Amgen’s Kyprolis in newly diagnosed multiple myeloma
  • BMS nivolumab data in 1L lung cancer (CheckMate-026)

The last two in particular seem to be causing a lot of hand-wringing!

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AACR Annual Meeting 2016 BannerOne of the hot topics at the forthcoming 2016 annual meeting of the American Association for Cancer Research (AACR) in New Orleans is likely to be CAR T cell therapy (Twitter: #AACR16).

Several research groups have shown impressive results in acute lymphoblastic leukaemia (ALL), but challenges remain in using adoptive cell therapy to treat other leukemias such as CLL, as we heard from Dr Porter at the recent BMT Tandem meeting. See post: Challenges and Opportunities of CAR T cell therapy in CLL. Perhaps more significantly, there’s a long way to go before CAR T cell therapies hit prime time in solid tumours.

What is fascinating is the pace of scientific research in the field. By the time the first CAR-T cell therapy is FDA approved, the second generation constructs used in them will most likely be obsolete.

This post reviews completely new research, which we’ve not written about before, that I expect we’ll hear more about at AACR, and discusses novel concepts about how to make CAR T cell therapy more effective in both leukemia and solid tumours.  It’s a good pre-AACR preparation for those interested in cancer immunotherapy and the emerging CAR T cell therapy landscape.

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Aggressive lymphoma… the very phrase is enough to send chills down your spine!

ASH Annual MeetingIn the past, much of the focus at previous American Society of Hematology (ASH) meetings in this area has focused on the myriad of chemotherapy regimens and dose/schedule optimisations that followed in trying to boost patient outcomes.

This year, I’m pleased to say that things have quite a different flavour with numerous new therapeutics and promising combinations in development.

Some of these are inevitably hypothesis testing, while others will be up-levelling to large randomised controlled multi-centre trials.

As part of our ongoing preview series, we take a look at the different categories to watch out for beyond chemotherapy.  These include monoclonal antibodies, antibody drug conjugates, targeted therapies and yes, even immunotherapies.

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Multiple myeloma (MM) has been very much in the news this week after the American Society of Clinical Oncology (ASCO) abstracts were released to much anticipation.

Myeloma is largely thought to be an incurable disease despite the option of an autologous stem cell transplant for newly diagnosed patients. That said, I have actually met some people who have had two or 3 transplants over several decades, a testament to their strength and fortitude in enduring such a challenging procedure.

This year, the news media have focused on elotuzumab (BMS/AbbVie), a CS1/SLAMF7 inhibitor that has previously shown clinical activity in earlier trials, after it was showcased in the ASCO Presscast last week. This why you see many articles on the data reported from this particular abstract.

New Orleans American QueenIt’s not the most exciting new data in this disease for me though, that honour goes to two other therapeutics of an entirely different kind. They come completely out of left field and what we saw over the last two months really caught our attention and may surprise you too.

Indeed, we saw hints of some of this data at the American Society for Gene and Cell Therapy (ASGCT) meeting last week in New Orleans.

To learn more about the exciting new developments in the field of multiple myeloma and what a leading thought leader had to say, you can sign in or sign up in the box below.

A regular reader of BSB wrote in asking for an update on Amgen’s blinatumomab, an anti CD3/CD19 bispecific antibody being investigated in B cell adult acute lymphoblastic leukemia (B-ALL) and Non Hodgkins Lymphoma (NHL). It has orphan designation for both indications.

Amgen acquired Micromet and their BiTE program way back in January 2012. At the time, the R&D head, Roger Perlmutter, referred to the exploratory phase II results as being a key driver for their interest in the technology. Like many, I too, was initially enthusiastic about the bispecific antibody when it was with Micromet, since those were very encouraging results in refractory adult ALL, a particularly hard to treat malignancy with a generally poor prognosis.

Unfortunately, since then we’ve heard very little about the program, which seems to have languished in the Amgen portfolio, a not uncommon occurrence when big Pharma/Biotech take over small biotech programs. In the meantime, chimeric antigen receptor (CAR) T cell therapies have arrived to much fanfare, and with it, even more dramatic results that have caught people’s attention.

Is there still a future for blinatumomab and BiTE technology?

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Chronic lymphocytic leukemia (CLL) and indolent non-Hodgkins Lymphoma (iNHL) have received significant attention over the last two years. More exciting new therapies than ever before – with multiple different mechanisms of action – have either recently come to market or are in development. There is an ongoing revolution in the CLL landscape and treatment of the disease, which above all else is good news for patients! As part of our ongoing longitudinal coverage, there’s a lot to discuss and catch up on in Chicago at the annual meeting of the American Society of Clinical Oncology (ASCO).

What’s different at ASCO this year?

Basically, a LOT more data – it’s almost a tsunami considering this is ASCO and not the American Society of Hematology (ASH) annual meeting!  I am excited to see that there is so much new data at ASCO. Yesterday, we highlighted 3 key sessions for multiple myeloma. For CLL/SLL and iNHL there are 9 – to put the sheer breadth of data and studies in context. This includes ongoing phase 1-3 trials, as well as new randomised controlled phase 3 studies that are now open and enrolling patients. If successful, some of these latter studies will play a crucial part in future registration packages to the Health Authorities. In the past, we have talked extensively about CD19 antibodies such as obinutuzumab (Gazyva) and BTK inhibitors such as ibrutinib (Imbruvica). Both of these drugs are now approved and available in the US.

Other therapies in development we have covered in the past have included PI3K inhibitors delta (idelalisib) and delta, gamma (IPI-145), as well as Bcl2 inhibitors (ABT-199 / GDC-0199), SYK inhibitors (fostamatinib and GS-9973), and CAR T cell therapies such as CTL019. To find out more about our insights on the ever-changing CLL landscape, you can sign in or sign up below.



“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

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One of the fun aspects of the American Society of Hematology (ASH) conference last month was interviewing several thought leaders and CEOs about the latest developments that were emerging rapidly almost every single day.  Now, some medical meetings can be rather dreary if there’s no new or exciting data to pique the interest of the foot weary attendees, who tend to run on coffee and adrenalin for four days, but this ASH was rather different.

Looking at the program the first morning, I realised that I hadn’t felt so much anticipation since the 1999 meeting, when the phase I imatinib (Gleevec) data was presented in the plenary session by Brian Druker.  This time around there was a lot of buzz in so many areas from CLL and NHL to myeloma and ALL, it was pretty exciting to run from session to and see many packed rooms filled with an air of expectancy.  One evening, I hesitated at the top of an escalator and dithered over which of three very interesting sessions to dash to, as a bunch of researchers crashed into me all distracted by the exactly same dilemma!

If many of us could have made one request of the ASH organising committee it was clearly start offering a virtual meeting for all the oral sessions, something ASCO do incredibly well.

At ASH if you miss a presentation, it’s gone forever.

This is quite a pain if you really wanted to see the data from Agent X in CLL, Compound Y in CAR T cells and Drug Z in myeloma, as well as the one you actually attended.  All those sessions ran simultaneously.  It also means the sessions are still running at 7pm (yes, they were still packed even at that hour!) and many of us had an early start with 7am sessions or meetings.

The huge distances between rooms (#blisterruns), coupled with a stubborn insistence in putting almost all the oral sessions on Monday and Tuesday, together with long waits between interesting sessions over the weekend, makes for a very frazzled and disjointed schedule. Patience and stamina are the name of the game here.

Despite scattered logistics, the conference was actually a lot of fun. If I had to compile a top 10 of key abstracts I really liked in New Orleans then it would take a long time, simply because there was so much new data requiring much agonising over what to leave out.

Stephan GruppThat said, one interview I particularly enjoyed was with Dr Stephan Grupp, a pediatric hematologist who is the Director of Translational Research, Center for Childhood Cancer Research at The Children’s Hospital of Philadelphia (CHOP).  By an odd quirk of the schedule, it seemed that he and I always seemed to be in the same sessions, although we actually spoke by phone afterwards, given the craziness in both our schedules.

There were two events in particular that were notable highlights:

  • A fascinating and well-thought out hour long seminar that Dr Grupp and Dr Elizabeth Shpall (MD Anderson) hosted on “Featured Topic: Chimeric Antigen Receptors (CAR): Driving Immunotherapy!” where they summarised the progress in this field in a lively, very fair minded and balanced fashion.
  • An oral presentation on the “Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019 cells) Have Long-Term Persistence and Induce Durable Responses In Relapsed, Refractory CLL” [Abstr #4162]

The lunchtime seminar was simply outstanding and incredibly educational, with attendees jam packed into a tiny hall they could probably have filled three times over. It was worth the registration fee for this one event alone, it was that good. Definitely one of my top 10 highlights.

The refractory pALL study was my favourite data from the conference, though it was sadly not in the plenary. Many attendees present in New Orleans whom I spoke to, however, clearly thought it was very worthy of a such a slot. The approach and results were groundbreaking and impressive.

If you are interested in reading the interview with Dr Grupp and our insights on this area, please sign in or sign up in the box below to continue.

The Inquirer yesterday reported on that start-up Juno Therapeutics (Juno) are now in control of a legal dispute between St Jude Children’s Hospital (St Jude) and the University of Pennsylvania (Penn) over chimeric antigen receptor (CAR) intellectual property that contributed to the development of CTL019, licensed by Penn to Novartis. Thanks to @lomu_j for sharing this news on Twitter.

According to the Inquirer, last month Juno entered an agreement with St Jude to commercialize their CAR T-cell technology, which gave them the right to “control, pursue and defend” the dispute between Penn and St Jude.  On December 18, Juno’s intervention was approved in Federal District Court in Philadelphia.

(Update Jan 10: Zack Seward (@ZackSeward) provides additional commentary on WHYY Philadelphia newsworks on “The high-stakes legal fight over a ‘cancer cure from Penn.’ He reports that St Jude have every confidence in their patent.


Subscribers can read my analysis of the case below.

Now that the last of the 2013 cancer conference season is finally over, we’re going to run a couple of post meeting summaries this week from ASH as a few subscribers have asked for the Cliff Notes version of what was hot – or not in the context of the market.

New treatments for Chronic Lymphocytic Leukemia (CLL) was one of the hot topics at the recent annual meeting of the American Society of Hematology in New Orleans.

Hot on the heels of Roche’s recent FDA approval for Gazyva (obinutuzumab/GA101) in CLL, other companies in the race to market including:

  • Pharmacyclics and Johnson & Johnson (ibrutinib)
  • Gilead (idelalisib, GS-9973)
  • Infinity (IPI-145)
  • AbbVie and Roche (ABT-199/GDC-0199)
  • Novartis (CTL019).

Here’s my subjective and personal assessment of the winners and losers based on the data presented:

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