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Immune checkpoint inhibitors that target CTLA4, PD1 and PDL1 can generate prolonged responses in a minority of patients, but the results so far in prostate cancer have been disappointing. Prostate cancer doctors have not been part of the excitement spreading through the cancer community like a “Mexican wave.”

Prostate cancer has not featured significantly in the cancer immunotherapy news recently, but that’s not to say there is not a lot going on. The phase 3 trial results of ipilimumab (a checkpoint inhibitor of CTLA-4) in the pre-chemotherapy setting of advanced prostate cancer (NCT01057810) are expected soon and there is also the eagerly awaited phase 3 trial of the PROSTVAC vaccine (NCT01322490).

Dr James Gulley ASCO 2015

At ASCO 2015, BSB interviewed Dr James L. Gulley, MD, PhD Chief of the Genitourinary Malignancies Branch and Director of the Medical Oncology Service at the National Cancer Institute (pictured above).

He talked about some of the cancer vaccine work he has done as part of the CRADA (Cooperative Research and Development Agreement) between the NCI and Bavarian Nordic, as well as strategies to help immunotherapy work in those tumors such as prostate cancer that are non-inflamed, where there may be an insufficient immune response for checkpoint inhibitors to work effectively.

Readers may recall we interviewed him at ASCO GU earlier year, “How to make non-immunogenic cancer sensitive to checkpoint inhibitors.” His outstanding work could shape the future of prostate cancer immunotherapy.

This post also includes additional ASCO 2015 commentary on from Dr Oliver Sartor, Professor of Cancer Research at Tulane University, who shared his perspective on the ipilimumab and PROSTVAC phase 3 prostate cancer trials that are due to readout soon.

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Chicago – it’s Monday at ASCO 2015, with a full day of symposia, oral abstracts and posters here in Chicago.

Yesterday in the Plenary Session here at ASCO, Dr Jedd Wolchok (Memorial Sloan Kettering Cancer Center) presented the results of the Checkmate 067 trial (LBA1) – the results of a phase III trial of nivolumab (NIVO) alone combined with ipilimumab (IPI) versus IPI alone in treatment naive patients with advanced melanoma. You can read more about this in our ASCO Day 3 highlights.

Dr Wolchok is pictured below, prior to presenting at the ASCO 2015 press briefing.

Dr Jedd Wolchok ASCO 2015 Press Briefing

Checkpoint inhibitors have been a real buzz at this meeting, but with the realization that they are not going to work in all patients, and other treatments are not going away… for all the promise there’s still a lot of work to do optimize cancer immunotherapy.

There’s also been a lot of talk at ASCO about PD-L1 as a biomarker, and if you haven’t already done so, do check-out Episode 2 of the Novel Targets podcast (The Immune Biomarker Show) that touches upon many of the key issues.

If you haven’t already done so, do check out yesterday’s post on the metastatic lung cancer session, including the AZD9291 vs. rociletinib race to market in T790M, because there was some interesting new data presented that will likely have an impact today.

What’s hot on Monday at ASCO 2015? This will be the last of our daily posts from ASCO 2015. Subs can login to read our highlights as the day progresses. We’ll update schedule permitting.

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Chicago – the cancer immunotherapy poster session yesterday morning was “mobbed,” that is the only word to describe it. I have never seen such a crowded poster session at any medical meeting before. It speaks to the huge interest in this growing field.

ASCO 2015 Cancer Immunotherapy Poster Session

It’s also a reflection that insights into the future direction of the field will be found in posters about preclinical and early work, rather than in oral presentations that reflect strategic decisions made a long time earlier.

We know checkpoint inhibitors work in many cancers, and a few more have been added to the list at this meeting. While that’s interesting, the real question is how do we increase the response rate and also get them to work in non-immunogenic tumors?

Yesterday in the poster session at ASCO, there was a poster that caught our attention on one approach that may achieve this. We briefly wrote about it in the ASCO Day 2 blog.

Also of note yesterday was that the new generic name for the PD-L1 checkpoint inhibitor from Roche/Genentech. MPDL3280A is now atezolizumab. A few presenters stumbled over the pronunciation, it was so new…… and all the z’s add to the trickiness!

As to what Day 3 at ASCO holds, we’ll be updating this blog during the day as our schedule permits.

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Chicago – after an evening of beer and networking at the unofficial ASCO15 Tweetup, the ASCO annual meeting, like a checkpoint inhibitor combination, releases the break and steps on the gas: the main data presentations start today. It’s “super saturday” at ASCO15.

Yesterday, the press had a preview of some of the cancer immunotherapy data to be presented this morning – we’ve shared our preliminary thoughts on this in yesterday’s ASCO15 Day 1 Cancer Immunotherapy post.

ASCO 2015 Day 1 Highlights

So what’s hot at #ASCO15 today?

We’ll be doing a rolling post throughout the day – when the opportunity presents we’ll provide some topline thoughts on sessions we’ve been to.

If you are here at ASCO, one #ImmunOnc presentation to watch out for this morning is the David A Karnofsky memorial award and lecture being given by Suzanne L. Topalian, MD in the main plenary hall (N Hall B1) at 11am.

From the recent presentations we’ve heard from her at AACR and AAI, her lecture entitled, “PD-1 Pathway Blockade – a Common Denominator for Cancer Therapy” should definitely worth listening to!

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Medivation-LogoNew Orleans – in today’s plenary session at the 2015 annual meeting of the American Urological Association (Twitter: #AUA15), Dr Celestia Higano (Seattle), presented the results of the STRIVE trial (NCT01664923) – a multicenter phase 2 study of enzalutamide (Xtandi) versus bicalutamide in men with nonmetastatic (M0) or metastatic castration-resistant prostate cancer (M1). These were men who were asymptomatic or mildly symptomatic.

Dr Celestia Higano STRIVE AUA 2015

Dr Higano noted that this was a very late breaking abstract; topline results were only announced a little over a month ago on April 2.

The TERRAIN trial also compared the efficacy of enzalutamide head-to-head against bicalutamide. We’ve updated our EAU 2015 TERRAIN post with the additional data presented here at AUA 2015 in New Orleans.

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New Orleans – one of the presentations of note at Immunology 2015 (the annual meeting of the American Association of Immunologists) was by Thomas J. Gajewski MD, PhD from the University of Chicago. His presentation on “Innate immune sensing of cancer via the STING pathway” was well worth the trip to New Orleans.

Presentation by Dr Gajewski at Immunology 2015

Readers may recall the post we wrote in March on “What is STING and why does it matter in cancer immunotherapy?” It followed the news that Novartis were collaborating with Aduro Biotech (NASDAQ: ADRO) on agonists that activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells.

I had the privilege to talk with Dr Gajewski (pictured below) after his presentation at AAI.

Dr Tom Gajewski AAI 2015

Excerpts from the interview will feature on Episode 2 of the Novel Targets podcast (@TargetsPodcast). (Do sign up for the Novel Targets Newsletter if you want to be among the first to know when this will air). Subscribers can read more from the interview below.

You should read and/or buy access to this post if you don’t know the answers to the following:

  • What role does the tumor microenvironment play in response to cancer immunotherapy?
  • How could the tumor microenvironment be a biomarker of response to checkpoint inhibitors?
  • Why target the STING pathway?
  • Reasons Novartis are collaborating with Aduro Biotech?
  • How may a STING agonist be brought to the clinic?

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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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Philadelphia – it’s the final day of the American Association of Cancer Research (AACR) annual meeting, and it’s been one of the best AACR annual meetings of recent years, with cancer immunotherapy very much at the fore.

This morning, the plenary session at the meeting was: Oncology Meets Immunology: Not Just Another “Hallmark.”

Cancer immunotherapy is changing the paradigm of cancer treatment in many ways, which is why the title of today’s plenary was clever….

Readers will be aware of the classic Hallmarks of Cancer paper (open access) by Douglas Hanahan and Robert Weinberg, which provides a framework for understanding how how tumors develop (e.g. sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis). This landmark paper provides a way to understand where new cancer treatments could act.

Today’s plenary featured four presentations from leaders in the field of cancer immunotherapy:

  • Engineering Improved Cancer Vaccines, Glen Dranoff, Novartis Institutes for Biomedical Research
  • Leukocytes as targets for therapy in solid tumors, Lisa M. Coussens, OHSU Knight Cancer Institute, Portland
  • Fatal Attraction: A new story featuring the immune system and pancreatic cancer, Elizabeth M. Jaffee, Johns Hopkins University, Baltimore
  • The mechanistic basis of cancer immunotherapy, Ira Mellman, Genentech, Inc. South San Francisco.

The first three speakers I have to say did not live up to the promise of their billing, spending far too much time on “My Pet Project,” delving into the weeds of the research from their lab or group, rather than putting the landscape in context, providing strategic direction of where things are going and including fair balance across the work in the field, which is what I expected a plenary presentation to be about.

One of our highlights of the plenary (and the conference) was the presentation by Ira Mellman, Vice President at Genentech who along with Dan Chen, Cancer Immunotherapy Franchsise Head at Genentech, are the author of the paper that is fast becoming the equivalent of the classic Hallmarks paper for Cancer Immunotherapy: Oncology meets immunology: the cancer-immunity cycle. (open access).

Dr Ira Mellman Dr Leisha Emens Dr Dan Chen AACR 2015

Earlier in the meeting, I had the privilege to chat with Drs Ira Mellman (pictured left), Leisha Emens (Johns Hopkins) and Dan Chen (pictured right) for the Novel Targets podcast. They are three of the many “rock stars” of the cancer immunotherapy world.

What were our highlights of AACR 2015?

We’ve carefully selected our Top Ten presentations of this year’s AACR for subscribers – Ira Mellman’s was one of them – but who are the others?  Some of them could be found outside the main sessions in the fringe rooms.

You can login in below or can purchase access to read them in the box.

For the week of the AACR meeting, there’s $50 off the price of a quarterly subscription, that will get you not only our post-AACR conference coverage, but access to the library of content we’ve written for example on immuno-oncology.

We’ll be at four meetings, including ASCO in the next two months, so to paraphrase Frank Sinatra, “The best is yet to come”…….

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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.

Subscribers can login to read more or you can purchase access below. This week in recognition of AACR, we are offering a $50 discount on the price of a quarterly subscription.

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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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