Biotech Strategy Blog

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

Posts tagged ‘NSCLC’

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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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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Yesterday saw the FDA approval of atezolizumab (Tecentriq) for the second-line treatment of metastatic non-small cell lung cancer (NSCLC) (link to company press release).  According to Genentech:

“This approval is based on results from the randomized Phase III OAK and Phase II POPLAR studies. The largest study, OAK, showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.”

The FDA approval is largely a broad one in 2L and 3L across PD-L1 expression and histologies [Link]:

“TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ.”

The approval was widely expected in light of the Phase III OAK trial data presented in the Presidential Symposium at ESMO16 meeting in Copenhagen.

Sign adjacent to #ESMO16 in Copenhagen

Sign adjacent to #ESMO16 in Copenhagen

Imagine hearing live about positive first-line data with pembrolizumab, with and without chemotherapy, negative data from nivolumab in the same setting, the 2L data for atezolizumab and two discussants drilling into both the data and broader impact of these studies to a jam packed audience that even included thought leaders from other tumour types who were also eager to hear the news. To say the atmosphere was electric would be a rather British understatement here.

We previously covered our initial impressions from that session [Link], but we also had the pleasure and privilege of interviewing a leading US thought leader in the lung cancer space after the session to garner his impressions of the data and also some perspectives on the key issues that the field is facing.

The pembro plus chemo data is already providing some controversy amongst various protagonists given there are a number of similar combination trials expected to read out over the next year to 18 months, plus much anticipation from analysts regarding the ditching of chemo for IO combos such as anti-PD–1 plus anti-CTLA–4 (BMS and AstraZeneca have keen stakes here), but what do thought leaders really think of that concept? Is that the slam dunk that many analysts seem to think it is?

This, my friends, is where things start to get a lot more complicated, akin to 3D chess in Star Trek.

What is happening now in advanced NSCLC is not how the market will look in a year or two. In many ways, the rate of approvals are outstripping the pace of science right now, but once the low hanging fruit is gone, competition will need to evolve in much more sophisticated and elegant levels.

With these questions in mind, we have a double header for you today – you can read on to find out more details from our latest though leader interview, supported by some insightful perspectives from a medical oncologist who treats lung cancer patients in private practice. Today’s post therefore covers some wide ranging discussions across the key issues in advanced NSCLC and it’s future direction.

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Please note that subscription prices will increase on Monday 24th, so if you’ve been on the fence about our upcoming coverage of #SITC2016, #ENA2016 (EORTC/NCI/AACR Mol Targets), #ASH16, #SABCS16 and #JPM17 then now is a good time to lock in at the current rates!

BioTwitter is all a-flutter today with the announcement from BMS that the CheckMate–026 trial in first line non-small cell lung cancer (NSCLC) comparing nivolumab (Opdivo) to chemotherapy did NOT meet its primary endpoint of progression-free survival (PFS).

The news was not entirely a surprise to us at BSB, here’s why…

Figurative statute representing Science on Holborn Viaduct in City of London.

Figurative statute representing Science on Holborn Viaduct in City of London.

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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

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Boston – Preclinical data for PF-06463922 (Pfizer), a next generation ALK inhibitor, with potency for all known Crizotinib ALK resistant mutants and ability to cross the blood brain barrier was presented today at the 2013 International Conference on Molecular Targets and Cancer Therapeutics co-hosted by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC).

In addition to being a competitor to other next-generation ALK inhibitors in development such as AP26113 (Ariad), LDK378 (Novartis) and alectinib (Roche/Chugai), PF-06463922 shows activity in both crizotinib-naive and crizotinib-resistant cells, so could end up being a replacement for crizotinib (Xalkori) front-line if clinical results confirm preclinical efficacy.

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