Biotech Strategy Blog

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

Posts from the ‘Melanoma’ category

Dr Mario Sznol

Dr Mario Sznol at SITC 2015 Patient Forum

Novel Immunotherapies and Combinations” was the title of the talk by Dr Mario Sznol (Yale) at the recent Immunotherapy Patient Forum co-hosted by Global Resource for Advancing Cancer Organization (GRACE) and the Melanoma Research Alliance at the 2015 SITC annual meeting.

At the forum, Dr Sznol also led a breakout session, where he reviewed what is melanoma, the treatment of primary melanoma and management of advanced disease, as well as answering questions from the patients and patient advocates.

Often at medical meetings you hear the results of a clinical trial that is but one piece of the jigsaw, so it was interesting to hear a more comprehensive overview of the disease.

Dr Sznol kindly spoke with BSB about his vision for the future of cancer immunotherapies. This post includes excerpts from the interview along with additional commentary.

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Oxford based Immunocore is an emerging UK biotechnology company that should be on your radar if you’re following companies such as Kite Pharmaceuticals and Juno Therapeutics. If it isn’t already you can expect to hear a lot more about them in the forthcoming year as they start clinical trials with the many leading global pharma companies who have already partnered with them.

Dr Namir Hassan, Immunocore

Immunocore is an immuno-oncology company with an innovative approach to targeting T Cell Receptors (TCR) using their proprietary ImmTAC (Immune mobilising monoclonal TCRs against cancer) technology platform.

Namir Hassan, D.Phil (pictured right) is Director of Translational Research and Head of Development at Immunocore. BSB met with him and Chief Business Officer, Eva-Lotta Allan at the company offices located in a science and business park near Oxford.

Immunocore recently raised $320M in Europe’s largest private life sciences funding. (Link to Press Release)

Earlier this year preliminary clinical data for IMCgp100 their first-in-class novel immunotherapy was presented at the annual meeting of the American Association for Cancer Research (AACR) in Philadelphia by Mark Middleton, Professor of Experimental Cancer Medicine at the University of Oxford.

In the interview, excerpts of which you can read below, Dr Hassan explained why their exciting and innovative approach that targets the T Cell Receptor is different from other companies in the field, what they have learned from the preliminary clinical data, and the potential immTACs may offer in combination with other cancer immunotherapies.

If you’re not a cancer immunologist, this type of science is complex, so the aim of the interview was to put into context the data already in the public domain and gain some insights into the excitement behind ImmTACs and what immunocore are doing. If you don’t understand the potential of TCRs and ImmTACs as immunotherapies, this post is for you!

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AAI LogoNew Orleans – At the 2015 annual meeting of the American Association of Immunologists (AAI) leading experts came together to share their insights on the Promise of Cancer Immunotherapy.”

The audience at #AAI2015, in an artic chilled hall, heard from an outstanding panel of speakers, many of whom flew in specially:

  • Immunologic Checkpoint Blockade: Combinations and Mechanisms, Jedd Wolchok (MSKCC)
  • Immune Checkpoint Therapy: Clinical Success and Next Steps, Padmanee Sharma (MD Anderson)
  • Improving Cancer Treatment Through Immunotherapy Combinations: Combination MAb Therapy: Dual tumor & Immune Targeting, Holbrook Kohrt (Stanford Cancer Institute)
  • Curative Potential of T-Cell Transfer Immunotherapy for Cancer, Steven Rosenberg (Surgery Branch, NCI)
  • PD-1 pathway blockade in cancer therapy: new frontiers, Suzanne Topalian (Johns Hopkins)
Dr Steven Rosenberg (NCI)

Dr Steven Rosenberg (NCI)

Cancer Immunotherapy is such a fast-evolving field that at Immunology 2015, we heard data that wasn’t at the annual meeting of the American Association for Cancer Research (AACR), just a few weeks ago.

Several presenters also put in context data that will published at the forthcoming ASCO annual meeting.

If you’d like to hear more about some of the checkpoint inhibitor data at AACR15, do listen to the first episode of the Novel Targets podcast (if you haven’t already done so).

It’s available as a free download on SoundCloud and on iTunes.

This post offers a top-line summary of some of the key messages we heard in the #AAI2015 symposium.

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With the news hot off the press at the 2015 annual meeting of the American Association for Cancer Research (AACR) that Merck’s pembrolizumab (Keytruda) beat out BMS’s ipilimumab (Yervoy) in advanced melanoma, quite a few readers wrote in asking whether this signals the end for ipilimumab?

The short answer is no, and here’s why…

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Philadelphia – at the 2015 annual meeting of the American Association for Cancer Research (AACR), new data was presented that showed checkpoint inhibitors have a greater effect when they work in combination, they may also offer a new effective treatment option in Triple Negative Breast Cancer (TNBC).

Are two checkpoints are better than one?

At AACR 2015, F. Stephen Hodi MD (Dana-Farber Cancer Institute) presented results, published simultaneously in the New England Journal of Medicine, that showed in advanced melanoma, combining two checkpoint inhibitors (nivolumab and ipilimumab) showed better results than with one alone (ipilumumab). The authors in their NEJM paper conclude:

The objective-response rate and the progression-free survival among patients with advanced melanoma who had not previously received treatment were significantly greater with nivolumab combined with ipilimumab than with ipilimumab monotherapy. Combination therapy had an acceptable safety profile.

What is the potential for checkpoint inhibition in TNBC?

Yesterday at AACR, Leisha S. Emens MD, PhD (Johns Hopkins) presented the results in TNBC from a phase 1 trial of MPDL3280A (Roche/Genentech), a checkpoint inhibitor that targets the PD-L1/PD-1 signaling pathway.

Dr Emens (right) is shown in the picture below presenting at an AACR media briefing moderated by Louis M. Weiner MD, Dr Hodi is pictured left.

AACR 2015 Press Briefing

The only currently available treatment for TNBC is chemotherapy, but sadly patients often do not live long, and rapidly progress. Progression-free survival (PFS) is estimated to be around 4 months in TNBC. This means there is a real unmet medical need for effective new treatments. The fact that cancer immunotherapy, and in particularly checkpoint inhibitors targeting the PD-L1/PD-1 signaling pathway may have potential in this disease is huge.

Cancer immunotherapy and in particular checkpoint inhibitors are a hot topic at AACR. In this post we look in more detail at the data presented.

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Philadelphia – the 2015 annual meeting of the American Association for Cancer Research (AACR) is in full swing, with over 18,000 attendees, it’s probably the world’s largest meeting dedicated to cancer research. The theme is “Bringing Cancer Discoveries to Patients.”

AACR 2015 Annual Meeting Philadelphia

I challenge anyone not to attend, and come away inspired with new ideas on how the field of cancer research will evolve in coming years.

At this year’s annual meeting, not surprisingly, cancer immunotherapy is one of the hot topics. Yesterday there was the simultaneous publication of two papers in the New England Journal of Medicine (NEJM) to coincide with data presented at the meeting.

Pembrolizumab (Keytruda)  for the Treatment of Non–Small-Cell Lung Cancer

The conclusion of the paper by Edward B. Garon, MD (UCLA) et al was that:

Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non–small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

The other paper published in the NEJM was for:

Pembrolizumab (Keytruda) versus Ipilimumab (Opdivo) in advanced Melanoma.

The conclusion of the paper by Caroline Robert, MD PhD, presented at AACR by Antoni Ribas, M.D., Ph.D.(UCLA) was:

The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.

AACR 2015 Press Briefing with Dr Topalian, Dr Ribas, Dr Garon

Dr Ribas (left) and Dr Garon (right) are pictured at an AACR media briefing chaired by Dr Suzanne Topalian (Johns Hopkins).

This year’s AACR annual meeting is to paraphrase Bertrand Tombal, “a Grand Cru year”. Not only in cancer immunotherapy, but in metabolism, epigenetics and advances in drug discovery.

We’re excited about the prospect of another three days at the meeting, but in the meantime in this post there’s some top-line thoughts for subscribers on some of the data that caught our attention over the weekend.

In recognition of AACR, there’s $50 off a quarterly subscription if you wish to purchase access (offer valid only during the week of the meeting – ends this Friday!)  If you’ve been sitting on the fence for a while wanting to try out BSB, now is a good opportunity to dip your toes in the water.

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Recently, Merck have been on a roll in the immuno-oncology space, with the announcement that their anti-PD–1 antibody, pembrolizumab (Keytruda), beat out BMS’s anti-CTLA4 antibody, ipilimumab (Yervoy) in a Phase 3 head-to-head frontline trial in metastatic melanoma. The two primary endpoints of OS and PFS were met and the trial will therefore be stopped early based on the IDMC recommendation. No further details are available until the presentation.

merck_logoThe data from the KEYNOTE–006 study is being presented at the annual American Association for Cancer Research (AACR) next month in the opening plenary session by Dr Antoni Ribas (UCLA).

While it’s nice to see evidence that one checkpoint inhibitor is potentially superior to another, in the long run, combinations are likely to be the best way forward.  This approach is more likely to yield improved responses in immunogenic tumours, but also to make non-immunogenic tumours more responsive, thereby improving patient outcomes further.

This begs the all important question – what hints from new emerging data can we glean that will help us figure out novel combination approaches with checkpoint inhibitors?

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Photo: National Institutes of Health

After last week’s post on therapeutic tumor infiltrating lymphocytes (TILs), we received a bunch of questions from readers.

I don’t have time to answer them all in detail individually (sorry!), but it does provide an opportunity to review the evolving landscape and address some of them within the latest article.

It seems to be a good time to take a broader look at T cell manipulation, especially as it pertains to the application of TILs, chimeric antigen receptors (CAR), and T cell receptors (TCR).

We’ve certainly come along way since the historic lecture in 1991 pictured right (photo: National Institutes of Health), but there’s still some way to go before the full potential of cancer immunotherapy is reached.

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Over the last two years we’ve written extensively about chimeric antigen receptor (CAR) T cell therapies, checkpoint inhibitors and immune agonists (stimulants), yet these aren’t the only novel immunotherapies that are being developed to target cancer cells.

One area that hasn’t received a lot of attention is adoptive cell transfer (ACT) and therapeutic tumour infiltrating lymphocytes (TILs).

  • What exactly are these approaches and what progress has taken place so far?
  • Where is this field going in the near future?

Rosenberg ASH14 TIL PresentationTo answer these questions, we put together a primer based on the groundbreaking research of Dr Steven Rosenberg (NCI Surgical Branch), and his invited talk at the recent American Society of Hematology (ASH) meeting.

As Rosenberg himself noted, what they’re doing is pretty daunting and yet, results so far have shown some impressive responses in some patients, especially those with metastatic melanoma, but other cancers have also responded well to this novel approach.

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Nature Cover Checkpoint InhibitorsIn a landmark publication today, the prestigious journal Nature includes five “Letters” regarding checkpoint blockade of the programmed death-1 (PD-1) receptor and its ligand PD-L1. It confirms the promise and potential of the emerging field of immuno-oncology to provide durable and long lasting responses in many cancers.

Readers of the blog will already have read about the stunning early data presented at ASCO this year for the engineered humanized antibody MPDL3280A (Genentech/Roche) in urothelial bladder cancer (UBC). In his Nature Letter, Thomas Powles (Barts) and colleagues sum of the significance of this data in the opening sentence:

“There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years.”

On the basis of this data, MPDL3280A received Breaththrough Therapy Designation from the FDA earlier this year.

Roy Herbst (Yale) and colleagues in their Nature Letter write about biomakers of PD-L1 inhibition and how their data “suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is reinvigorated on antibody treatment.

At the recent annual meeting of the Society for Immunotherapy of Cancer (SITC), Dr Herbst gave one of the best presentations of the meeting, in which he discussed Personalized Immunotherapy for Non-Small Cell Lung Cancer.  His top ten lessons learned kept the audience’s attention throughout.

In this excerpt from an interview he kindly gave BSB afterwards, he talks about the promise of cancer immunotherapy in lung cancer:

 

Tomorrow is the Thanksgiving holiday in the United States, so this will be the only post this week. Thanksgiving is a good time to take a moment out of the hectic life we all live to “smell the roses” and express gratitude for all the positive things around us.

Next week sees the start of the American Society of Hematology (ASH) annual meeting in San Francisco. The cancer conference circuit seems to roll quickly from one meeting to the next at the moment. There’s a lot of promising data, and while we can’t discuss the data before the meeting due to ASH embargo restrictions, next week we will be highlighting some of the presentations we are particularly looking forward to.

Happy Thanksgiving!

Subscribers can login below or you can purchase access to read more detail about all five Nature Letters, and their implications for the emerging field of immuno-oncology.

Tower of London Field of Poppies

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