Biotech Strategy Blog

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

Posts tagged ‘lung cancer’

MYSTIC Interim Analysis July 2017 shows PFS Miss

There has been considerable focus on the impact of cancer immunotherapy and checkpoint blockade in particular in non-small cell lung cancer (NSCLC) of late, with approval of several agents in the 1L and 2L metastatic setting, as well as positive results reported in stage 3 unresectable disease earlier this year.

To date, the approvals have focused on monotherapies in second-line (nivolumab, pembrolizumab and atezolizumab) allcomers, as well as in 1L in two cases i.e. for people who are PD-L1 High expressers (≥ 50%) for pembrolizumab or allcomers in combination with chemotherapy (pembrolizumab).

Today as part of their 2Q earnings call details, AstraZeneca ($AZN) announced that the MYSTIC trial exploring the combination of the anti-PD-L1 antibody, durvalumab (Imfinzi), plus anti-CTLA–4 antibody, tremelimumab, unfortunately missed the interim endpoint of progression-free survival (PFS).

This is the first dual IO-IO combo readout in this setting and while disappointing, the results aren’t entirely surprising, as regular readers will no doubt realise.

We are now awaiting several other trial readouts in 1L NSCLC, including Merck’s phase 3 confirmatory trial for pembrolizumab plus chemo and Genentech/Roche’s IMpower150 trial, which explores atezolizumab in combination with chemotherapy, with and without the anti-VEGF inhibitor, bevacizumab (Avastin).

For historical reference, we originally wrote up our perspectives on the 1L NSCLC landscape in January this year then followed that up with a provocative post outlining out predictions on what to expect earlier this month, including the projected miss in PFS for AstraZeneca’s IO combo.

So what does this latest data mean for AZN?

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Can AstraZeneca leapfrog the competition in lung cancer AGAIN?

Until recently, we followed the race to market in EGFR T790M lung cancer with Clovis’s rociletinib and AstraZeneca’s osimertinib (Tagrisso).  In phase 2, AstraZeneca caused quite a stir when they came from behind and leapfrogged their biotech rival with a large global randomized controlled trial seemingly out of nowhere.  They never looked back.

Can they do the same thing with durvalumab (Imfinzi), one of their IO therapies that targets PD-L1?

If there’s one thing that many astute observers of the IO space have learned this week it’s that irrational exuberance and the hopeful sentiment that ‘everything’ will just tweak the immune system and work positively no matter what has thankfully come to an end.

We’ve seen several highs and lows already with Merck’s pembrolizumab gaining accelerated approval in 1L NSCLC in allcomers when combined with chemotherapy and AstraZeneca reporting positive phase 3 data for durvalumab in unresectable (stage 3) NSCLC based on meeting the study endpoint (PFS).

There is much to be learned because the nivolumab disaster in 1L NSCLC last year was not a singular aberration given that durvalumab has seen some missteps in the past and even atezolizumab had some unexpected news with urothelial cancer this week (Check out our insights), as compared to chemo in the second line setting. Just like mutations, there will be many more to come, perhaps even some additional ones before the year is out.

What about today’s news from AstraZeneca in unresectable NSCLC?

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Asking Good Questions is both an Art and a Science

The recent PARP inhibitor data has stirred up a lot of interest amongst BSB subscribers (See post: PARP! PARP! what’s hot in ovarian cancer at SGO and AACR?).

So, rather than do another AACR 2017 Preview (more coming next week!), it seemed timely to take a look at some of the interesting questions we’ve received from subscribers.

Five questions have been selected for answer in this week’s BSB reader Q&A. We don’t award prizes if your question is selected, nor do we name who asked the question, but everyone benefits when interesting questions are asked and we can all learn from each other.

As author Thomas Berger aptly said:

“The art and science of asking questions is the source of all knowledge.” 

What differentiates many world class cancer researchers is frequently the scientific questions they ask in their work. The same holds true if you are a C level executive or a journalist. The quality of the answer you obtain is often dependent on the quality of the question you ask.

We hope that being better informed about the issues and topics we write about on BSB will enable subscribers to ask better questions, and in the process make better decisions.

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AACR 2017 Preview 1

In the first of our 2017 AACR annual meeting previews, we are taking a look at a particular theme that we expect to hear much more about over the coming months.

Washington DC cherry blossoms

In order to make something better than what it is, we first need to step back and understand the various factors that underpin it. To do otherwise is akin to the proverbial throwing of mud at the wall and hoping something sticks.

Trying things out just because they seem like a good idea or that’s all you have in your pipeline doesn’t really inspire the greatest of confidence in a clinical trial’s success.

This is also where several factors including tumour biology, cancer genomics, biomarkers, and acquired resistance can intersect to produce some intriguing results.

Please note that our Conference Preview series are never random.  When looking at the abstracts as a whole, we try to organise them around a particular scientific theme or a tumour type. The idea here is that it makes it much easier for our readers to see and grasp emerging concepts and trends. It’s also a deeper dive into the whys; things happen for a reason – why is that?  What can we learn from the process?

These are also not random selections from say, publicly traded or private companies, big or small caps.

It does take more time to roll thematic articles out, but the advantage is that over the course of the next two weeks readers will be better equipped to get a grip on the meeting ahead of the event.

Indeed, a couple of subscribers even told us last year they learned more from our in-depth previews than they did from the meeting itself because it’s easy to miss the important things or become ‘bigly overwhelmed’ as one bio fund manager explained to me.

Strategically, we’ve taken one specific theme today and explored what we can expect based on what we have learned to date, and looked at how that will potentially impact a few things going forward.

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Journal Club – February 2017

The huge pile of interesting scientific papers yet to be read seems to breed overnight and one constantly feels like they’re 2,000 articles behind, even with spending Friday mornings attacking them with gusto.

This was as true in my PhD days as it is now. For a scientist, these represent a lifeline and an important necessity, rather than a luxury.

In the last journal club posting we covered some hot topics in cancer immunotherapy, so this one covers a very different topic, namely targeted therapies.

It’s a good time for a new journal club post, where we tackle some of the recent published literature in oncology and highlight some important new findings that could have an impact on cancer research and development.

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Can we expect more surprises in 1L NSCLC?

Challenges and Opportunities in the evolving 1L NSCLC Landscape

Rolling English Landscape in Devon

Following a series of events – from BMS’s failure with nivolumab monotherapy… to Merck’s sudden announcement to file their combination of pembrolizumab plus chemotherapy… to AstraZeneca’s delay of the MYSTIC trial exploring durvalumab plus tremelimumab this week, there’s never a dull moment in lung cancer!

So can we expect some more surprises in store in 1L NSCLC?

I say yes we can!  

The big questions are what are they and what impact will they have?

2017 is ironically, the year of the Rooster – so who’s going to crow loudly at dawn and who is going to get strangled in the process?

In the world of cancer research it is unlikely that everything wins or is successful, so figuring out the early signs and hints is an important part of the process.

One thing I learned early in this business is that it pays for companies to be humble, flexible and open minded rather than arrogant and dogmatic in their thinking… otherwise you can easily be blindsided.

There were a few examples of that in oncology R&D last year, a repeat could very well follow in 2017 for the unwary.

Here we look at 1L NSCLC in the context of multiple phase 3 trials that are slated to read out… from AstraZeneca, BMS, Merck and Genentech.

If you want to know what the potential impact of these events are on the landscape, including what we can expect from MYSTIC, CheckMate-227 and several others, then this is the post for you because some surprises are likely in store.

We cut through the chase to explain the what and the why in clear simple language.

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ESMO16 Day 3 Daily Digest

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.

nyhavn-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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ESMO16 Preview 1 Novel Target Data Offers Potential to Overcome Barriers to Cancer Drug Resistance

September 1st… as the hot summer floats away from London town and cooler autumn days draw in, it’s time to think about the upcoming fall cancer conference season – it’s quite a busy one this year!

In the coming weeks, I will be rolling out our series on the ESMO 2016 Previews (Twitter #ESMO16) and taking a more in-depth look at various topics of interest. The Copenhagen meeting is later than usual and also more compressed, with numerous sessions now held simultaneously. It used to be that you could take a break between key sessions, but not any more – there’s a lot going on this year.

View of Thames BarrierOne of the things that jumped out to me from a preliminary review of this year’s hectic ESMO program is an interesting novel target that had some early preclinical data at AACR, but that sadly got lost in the tsunami of data there.

It is good to have that reminder and be able to return to it in the context of broader data because overcoming barriers to drug resistance with targeted therapies is still an important issue that is worth researching.

You likely won’t see it in many analyst reports or previews, however, although it’s a hidden gem of great interest and well worth exploring in terms of what we know so far. This means that readers will be both prepared and intrigued – don’t be surprised to hear about some BD&L deals in this niche in the future.

Curious? Subscribers can go here now to get all the details…

Contemplations on ASCO Lung Cancer Data with Dr Stephen Liu

Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Morgan Grafitti Wall

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

  • What can we do to help them?
  • Which combinations look more encouraging?
  • Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents.  At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article.

Future of Cancer Immunotherapy Biomarkers

Biomarkers are a hotly debated topic at the moment within the cancer immunotherapy field.

At the recent Society for Immunotherapy of Cancer annual meeting (SITC 2015), there was even a debate with industry representatives arguing the “pros” and “cons.” Daniel Chen, MD PhD from Genentech (pictured right) argued “pro” and Steven Averbuch MD (pictured left) from BMS argued “con.”

SITC 2015 Biomarker Debate

The challenging question for anyone at the moment is if your Parent, Spouse or Best Friend were PD-L1 negative, would you still want them to receive a PD-1/PD-L1 checkpoint inhibitor (presuming it was indicated for the disease) and have a chance of a response, even if their PD-L1 negativity would suggest only a slim chance of responding?

AT SITC 2015 we spoke with an industry expert who offered insights into a leading company’s biomarker strategy and what the future may look like in 5-7 years time.

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