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European Lung Cancer Conference 2016

European Lung Cancer Conference 2016

Geneva – At the 2016 European Lung Cancer Conference (ELCC) today, one of the highlights to watch out for is the presentation of first-line data for AstraZeneca’s ($AZN) third generation EGFR inhibitor osimertinib (Tagrisso), formerly known as AZD9291.

At 3.30pm in Geneva (9.30am on the East Coast of the United States), Dr Suresh Ramalingam (Winship Cancer Institute, Emory) will present updated data from two expansion cohorts of the AURA phase 1 trial (NCT01802632) with updated results on the use of osimertinib in the first-line setting:

LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts. S. Ramalingam, J.C.-H. Yang, C.K. Lee, T. Kurata, D.-W. Kim, T. John, N. Nogami, Y. Ohe, P.A. Jänne

Do follow tweets from the conference (#ELCC16).

As Dr Ramalingam noted in a press release issued by the European Society for Medical Oncology (ESMO):

“The overall response rate was among the best reported for first-line therapy of EGFR mutated NSCLC. The PFS results are exciting, well exceeding the historical control rates of 10 to 13 months with first or second generation drugs. Many of the patients have not had disease progression on the study and are still benefitting from treatment.”

Readers will recall osimertinib was approved by the FDA last November (link to press release) for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who test positive for an epidermal growth factor receptor (EGFR) T790M mutation following prior treatment with an EGFR tyrosine kinase inhibitor (TKI).

Nearly two-thirds of patients who receive an EGFR-TKI develop a T790M mutation, and until the approval of osimertinib, there were no approved treatment options.

I vividly remember being in the audience at the European Cancer Congress in Amsterdam back in September 2013 and listening to Professor Malcolm Ranson (Christie, Manchester) present the first clinical data from the phase 1 study, which at that time was only a single center. See post: ECCO 2013: AZD9291 shows early promise in NSCLC.

Dr Ross Camidge (Denver), who was the discussant in Amsterdam, concluded his discussion with a picture of the first step on the moon. Cancer metaphors around the moon and moonshots have since become overused, but I think this one was justified at the time:

“By addressing acquired resistance at the molecular level potentially creating one small step in the EGFR treatment paradigm, third-generation inhibitors like 9291 are likely to represent one giant leap forward in the treatment of EGFR mutant disease.”

~ Dr Ross Camidge at ECC 2013.

Whatever the role we play in cancer drug development, and most of us are but bit players, we live for moments like that. Dr Camidge’s visual metaphor remains etched on my memory as a landmark moment when all in the audience saw the first glimpse of a drug that could make a difference.

We’ve been following the development of osimertinib over the past 3 years and the race to market with Clovis Oncology’s rociletinib (formerly known as CO-1686). See e.g. AstraZeneca ramps up AZD9291 lung cancer clinical development, AstraZeneca leaps over Clovis with AZD9291 data at World Lung Conference.

Looking back, when you compare the development of osimertinib to rociletinib, it is a “Tale of Two Cities,” to paraphrase the title of a novel by Charles Dickens.

In a recent article (open access) published in Annals of Oncology, Dr Antoine Yver, Senior VP at AstraZeneca described how fast the development of osimertinib was:

“The development programme for osimertinib is the most rapid to date, taking just 24 months from filing the FDA Investigational New Drug Application to submitting the FDA New Drug Application and just 2 years 8 months and 1 week from the first patient dosed to the first approval.”

To put this in context, the speed of the osimertinib development rivals – and perhaps even just beats – the accelerated development of imatinib (Gleevec) by Novartis from Feb 1998, when the first patient was dosed, to approval in May 2001, a tremendous achievement.

Key to AstraZeneca’s success was the company’s previous experience in bringing gefitinib (IRESSA) to market in EGFR lung cancer.

The development of osimertinib by AstraZeneca offers a new case study to other companies in how to bring a drug to market.

Sadly, the drug development by Clovis Oncology offers the exact opposite, as evidenced by the recent meeting of the FDA Oncology Drugs Advisory Committee, which recommended (12 to 1) against accelerated approval of rociletinib for the same indication as osimertinib. See FDA ODAC meeting briefing documents (link).

So what do we learn from the first-line osimertinib data presented at European Lung?

Dr Pasi Jänne at ASCO 2014

Dr Pasi Jänne, Dana-Farber Cancer Institute pictured at ASCO 2014

I spoke with the senior author of the LBA_1 PR abstract at European Lung, Dr Pasi Jänne, who is Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute (DFCI) and Professor of Medicine, Harvard Medical School about the significance of the data presented at European Lung.

During the interview, excerpts of which I’ve posted for subscribers, we touched on acquired resistance to osimertinib and whether rociletinib has any future in the treatment of EGFR positive NSCLC.

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Lemons Villa BorgheseThe discovery of a novel target in castration-resistant prostate cancer (CRPC) and the potential of drugs targeting this to delay or overcome adaptive resistance is the subject of today’s post.

Followers of the prostate cancer field know that one of the challenges with drugs such as enzalutamide and abiraterone is that patients stop responding to them over time and they develop acquired resistance.

So imagine that you could give a drug that is not only an effective anti-cancer agent in patients with acquired resistance, but might then allow those treatments to be effective a second time around.  A recently identified druggable target means this is now a possibility.

Of course, it’s early days yet, and the preclinical work has yet to translate into humans, but it’s not hard to see the commercial implications in the prostate cancer landscape for companies such as $MDVN, $JNJ, $TKAI, Bayer and anybody else who wants to be a player.

Interested? Subscribers can login to read more or you can purchase access below. This post is Day 3 in our Road to AACR 2016 series.

King Kamehameha Statue Honolulu HI

King Kamehameha Statue, Honolulu HI

Honolulu: we’re continuing our coverage of the 2016 BMT Tandem meeting with a thought leader interview about a novel cancer immunotherapy approach that we’re excited about.

The cancer cell therapy landscape is still vastly uncharted territory in many respects.

The first CD19 targeted CAR T cell therapies expected to reach the market in 2017 are unlikely to be best-in-class, which leaves the commercial door open for other approaches that may be better, cheaper or more accessible.

If you are in the CAR T cell therapy space, there are plenty of competitive threats on the horizon, and the novel approach discussed in this post is one of them!

We’d heard a little about it, but hadn’t explored the concept in any detail, so were delighted to talk with a leading expert at the BMT Tandem meeting in Honolulu.

Subscribers can login or you can purchase access to read more about a cell therapy that could offer the benefits of a CAR without the need for genetic modification.

Honolulu: Yesterday we learnt the sad news that Dr Holbrook Kohrt (pictured) had died.

Dr Holbrook Kohrt He was a Stanford hematologist/oncologist and rising star in the cancer immunotherapy field. Our thoughts go out to his family and friends.

I had the privilege to interview him last May at the Immunology 2015 meeting in New Orleans. His voice lives on in Episode 6 of the Novel Targets Podcast. One area of Dr Kohrt’s research was in combination immunotherapies, and how we can optimize efficacy, while avoiding significant immune adverse events.

So are checkpoints playing with fire when given in combination?

That was one of the provocative questions to come out of a scientific session entitled, “Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a platform for Novel Immunotherapies” at the BMT Tandem meeting in Hawaii last weekend. The session, chaired by Miguel-Angel Perales (@DrMiguelPerales) from Memorial Sloan Kettering Cancer Center, was both informative and interesting.

All the presentations were excellent, but one by Philippe Armand from the Dana-Farber Cancer Institute in Boston, “Checkpoint Blockade in SCT, Data & Hope, Promise & Peril” stood out for me. Dr Armand discussed checkpoint data pre and post stem cell transplantation and offered a perspective I had not heard before.

One of the provocative questions it raised was could checkpoints be playing with fire in some patients? Dr Armand kindly spoke with BSB after his talk.

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Honolulu: At the BMT Tandem meeting that ended yesterday in Hawaii, one of the hot topics was CAR T Cell Therapy. This should, perhaps, come as no surprise to readers given that bone marrow transplanters are not only the investigators doing the clinical trials, but will be the initial target market for this product.

Dr Micheal JensenOne of the pioneers in the development of adoptive cellular therapy is Michael Jensen (pictured) who is Director, Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute (SCRI) and the Sinegal Endowed Professor of Pediatrics at the University of Washington School of Medicine. Dr Jensen is also a scientific co-founder of Juno Therapeutics, Inc.

He’s been doing research in the field for over 20 years, and told me that not so long ago there would only be a handful of people in the room for a CAR T cell presentation!

In a plenary scientific session at the Tandem meeting, he presented to over 3,000 attendees on “CD19-Specific CAR T Cells as a Post-ALLO HSCT Relapse Salvage Therapy.”

After his presentation, he kindly spoke with BSB. This post describes some of the key take-homes from his talk.

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Dr David Porter, U Penn

Dr David Porter, U Penn

Honolulu: The BMT Tandem meeting kicked off yesterday with an excellent plenary session on “CAR T Cell Therapy: CD19 and Beyond.” The three presenters were:

  • David Porter (University of Pennsylvania) CAR T cells for Leukemia
  • Martin Pule (UCL) Building a CAR
  • Michael Jensen (Seattle Children’s) CD19-Specific CAR T Cells as a Post-Allo HSCT Relapse Salvage Therapy

Dr Porter (pictured) is Director of the Blood and Marrow Transplant Program at the University of Pennsylvania. I spoke with him after his talk. This post gives a quick overview of some of the key points I took away.

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North Shore Surf Shop SignAloha! The BMT Tandem meeting (Twitter #BMTTandem16) is underway in Honolulu, and we’re looking forward to the scientific presentations that start tomorrow, Thursday.

This preview highlights some of the presentations that may be of interest to subscribers at the meeting over the next 5 days when they’re not surfing waves at the North Shore! The meeting ends on Monday Feb 22.

If you can’t make it to Hawaii, then I expect the BMT community will be sharing updates from the meeting via Twitter. Do follow: @DrMiguelPerales, @DrKomanduri, @sgiraltbmtdoc, @DrMvandenBrink, @BldCancerDoc, @MSKBMTTandem & others (this is not intended to be a definitive list, only a starting point).

We won’t be doing a daily blog, but will be generating some commentary and analysis, as the opportunity presents.

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Aloha! If you have plans to be in Honolulu next week for #BMTTandem16, then one of the “must do” sights is the walk to the top of Diamond Head. It towers over Waikiki and is a major landmark for anyone travelling in an easterly direction.

Waikiki from Diamond Head

One way to get there is to start early and take the #23 The Bus ($2.50 fare, exact change) from Ala Moana & Waikiki to the state park entrance. The path starts off deceptively easy, kicks in with some uneven surfaces and hits you with a pile of steps near the top. Sensible shoes, water and sunscreen recommended.

The spectacular views at the end are well worth it, especially if you catch the sunrise/early morning light and manage to avoid arriving at the summit at the same time as busloads of Japanese tourists with the same idea. It’s a popular attraction!

One of the reasons for going to the top of hills and mountains is to see the “big picture” of the landscape below. In writing and reporting on the latest innovations in biomedicine, we often focus on the results of one trial or news from one company; yet it’s also important to see how the pieces of the jigsaw fit together.

That’s why pharmaceutical marketers and new produce development specialists often commission custom reports that review the strategic landscape in a therapeutic area.

As part of our coverage of #BMTTandem16, we’re taking a look at some of the strategic trends and drivers in the Graft versus Host Disease (GvHD) space.

It’s an area of unmet medical need and market opportunity.

Anyone with an interest in allogeneic “off the shelf” CAR-T cell therapy should already appreciate the significance of GvHD as a potential complication. If you don’t, then you’ve not been reading BSB…

In case you missed it, do listen to Dr Marcel van den Brink talking about GvHD on the Novel Targets Podcast. (Episode 9: Targeting the Microbiome)

This post is not intended to be a substitute for a landscape report, but offers some top line thoughts on some of the strategic drivers to look out for.

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Aloha! It will soon be time to pack your Hawaiian shirts for the forthcoming BMT Tandem Meeting in Hawaii (Twitter #BMTTandem16 – what a long hashtag!!)

ASBMT_2016WebBanner_b

Commonly known as “Tandem,” it’s the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT).

Hawaii is great location for a meeting in February, and one that I’m sure will generate a lot of envy for those who can’t attend and are stuck in the winter cold and chill. Who said we don’t go the “extra mile” for BSB subs?

One of the presentations I’m looking forward to hearing at Tandem is by Ann Leen, PhD, who is an Associate Professor at Baylor College of Medicine.

Dr Leen will be talking about “Immunotherapy for Lymphoma using T cells Targeting Multiple Tumor-Associated Antigens.

At last December’s ASH annual meeting, Dr Leen presented preliminary data with this novel approach in patients with Hodgkin’s Lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). After her ASH presentation, she kindly spoke to BSB.

This post is part of our post-meeting ASH15 coverage, and our ongoing coverage of some of the exciting developments in immuno-oncology.  In case you missed it, do check out the ASH interview with Seattle Genetics CEO Clay Siegall, PhD.

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Streets of San FranciscoOne of the interesting immuno-oncology presentations at the recent ASCO Genitourinary Cancers Symposium held in San Francisco from Jan 7 – 9, 2016 was presented by Dr Matt Galsky (Mount Sinai, New York).

Dr Galsky presented the results of a phase II trial of gemcitabine plus cisplatin plus ipilimumab in patients with metastatic urothelial cancer: HCRN GU-148 (Abstract 357).

The trial failed to reach its primary endpoint of showing a 20% increase in 1 year overall survival by the addition of ipilimumab compared to historical data for Gem + Cis in this patient population.

Many in the media don’t write up what is in essence “negative” data, but this trial is highly informative for those with an interest in urothelial cancer and in the optimal strategy for cancer immunotherapy. The GU16 discussant Dr Elizabeth Plimack (Fox Chase) raised many questions that merit consideration by those in the field.

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