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

Posts tagged ‘Lung Cancer Immunotherapy’

Copenhagen – Day 3, Sunday at #ESMO16 was a day to remember on many levels. From being carried forward by a rush of people as a massive crowd was finally let into the Presidential Symposium…

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

Large crowd of delegates wait patiently to enter ESMO16 Presidential Symposium

…to hearing an outstanding discussion of data by one of Europe’s leading lung cancer experts, Professor Jean-Charles Soria (@jsoriamd). He was insightful, engaging, as well as funny in places and was a hard act to follow…

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

Prof. Soria discussing KEYNOTE-024 data at ESMO 2016

The end result was a day to remember, most significantly it was one where we heard data that will change the standard of care in front-line non-small cell lung cancer (NSCLC), with the expected approval of pembrolizumab (Keytruda) for patients whose tumors have a high expression of PD-L1 (50% or more).

We’re continuing our daily digest of highlights from sessions we attended at the 2016 European Society for Medical Oncology (ESMO) Congress here in Denmark.


The sun has not shone much here in Denmark during the Congress, the above photo of Nyhavn was taken just before the meeting started, but the data at ESMO16 has shone brightly with two more publications online in The New England Journal of Medicine to coincide with their presentation in Sunday’s Presidential Symposium:

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer (NEJM link)

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck (NEJM link).

This mini-series of daily digests over the 4 days of the Congress is intended to give subscribers a finger on the pulse on some of the buzz and conversation…. and occasionally an alternative perspective. We’ll be writing more detailed posts as part of a post-conference series.

In this post, @MaverickNY offers her topline impressions of the lung cancer data presented in the Presidential Symposium, how this will change how some patients are treated, and the resulting impact on the lung cancer landscape. Cancer Immunotherapy continues to drive changes in clinical practice, and is doing so at a very remarkable pace.

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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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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.

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

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.

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