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Posts tagged ‘Lung Cancer Market’

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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European Lung Cancer Conference 2015Geneva – at the 2015 European Lung Cancer Conference today, Pasi A. Jänne, MD, PhD presented updated progression free survival and duration of response data for the phase 1 AURA trial of AZD9291 (AstraZeneca) in patients with EFGR-TKI-resistant advanced non-small cell cancer (Abstract LBA3).

Dr Jänne (pictured below at ASCO 2014) is Director, Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

Dr Pasi Jänne ASCO 2014

It’s hard to believe that it is only about two years since the first patient was enrolled in the phase 1 AURA trial of AZD9291, a third generation EGFR inhibitor. If the FDA regulatory submission takes place, as expected, in the second quarter of this year, then the drug could be approved for sale in the United States before the year end.

It has been fascinating to watch the race to market between rociletinib (Clovis Oncology) and AZD9291. It’s likely both could be approved in the United States before the year end.

That would be great news for lung cancer patients, given the absence of any approved therapy for patients who develop a T790M mutation and become resistant to EGFR inhibitors, such as Tarceva and Iressa.

Readers will know that we have been following the phase 1 AURA trial of AZD9291 since ECCO 2013 in Amsterdam, when the first clinical data was presented.

AstraZeneca are to be congratulated on what is a case study of rational scientific drug development; their path to market strategy highlights the benefit of well-designed early clinical trials. AZD9291 may end up receiving regulatory approval less than three years from the start of the first in man trial – that’s tremendous!

I had the privilege to interview Dr Jänne at ASCO last year, and again earlier this week, before he left Boston for Geneva and chatted with him about his AZD9291 presentation at European Lung.

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With all the heightened interest in checkpoint inhibitors of late, I wanted to continue my series on what did we learn from the updated data at ESMO that was different from ASCO? Last week we discussed gastric and bladder cancers, this week it’s the turn of lung cancer, or more specifically, non-small cell lung cancer (NSCLC).

By chance, some interesting announcements have also happened since ESMO with the third quarter earnings calls going on from the main players in this space, which also add colour to the developments in this niche. BMS, for example, announced that they expect their rolling NDA for Opdivo in lung cancer to be completed before the year end and will be presenting the CHECKMATE 063 data this week, while Merck announced their Breakthrough therapy designation for Keytruda in lung cancer this morning.

All in all, this makes the lung cancer space a lot more exciting than it was at ASCO, where the response to the data was fairly muted.

To learn more about the updated ESMO data and the impact of the recent announcements in lung cancer, you can sign in or sign up below to read our insights.


AZD9291 AURA Study World LungSydney – AstraZeneca AZD9291 is now ahead of Clovis Oncology CO-1686 in the race to bring a third-generation epidermal growth factor receptor (EGFR) inhibitor to market that targets the T790M resistance mutation.

That is the conclusion I took from the updated preliminary phase 1 data for the AURA study of AZD9291 in non-small cell lung cancer (NSCLC) presented today at the 15th World Conference on Lung Cancer in Sydney, Australia.  Clovis Oncology presented updated phase 1 data for CO-1686, their third-generation EGFR inhibitor, in Sydney earlier this week.

EGFR inhibitor resistance occurs in most NSCLC patients within 10-11 months with approx. 50-60% developing a gatekeeper mutation called T790M.

There are no approved treatments for NSCLC patients with T790M mutations, so this unmet medical need represents a large commercial market opportunity.

Why do I think that AstraZeneca are now ahead of Clovis Oncology and what does the World Lung data show for both drugs?

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