Biotech Strategy Blog

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

Posts tagged ‘checkmate 227’

Yesterday afternoon BMS provided an announcement and update on the controversial phase 3 CheckMate-227 trial in first line non-small cell lung cancer (NDCLC).

Lightning bolt

Does lightning strike twice?

This large study compares the combinations of nivolumab with either ipilimumab or chemotherapy to chemotherapy alone in both squamous and non-squamous patients with previously untreated advanced disease.

Ahead of the data presentation what can we expect and what will the impact be on the broader landscape?

There is no doubt that BMS have had a chequered history in lung cancer since the miss with the earlier CheckMate-026 study. Is their run of missteps over or can we expect yet more controversy to befall them?

In our latest analysis we take a look at what going on in this niche.

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Chicago June 3, 2018: The data for the phase 3 KEYNOTE–042 trial has just been presented in the plenary session of the 2018 annual meeting of the American Society for Clinical Oncology (#ASCO18).

Data for this positive phase 3 study was presented by Dr Gilberto Lopes (@GlopesMd), Associate Professor at the Sylvester Comprehensive Cancer Center at the University of the Miami.

The trial in previously untreated patients with metastatic non-small cell lung cancer (NSCLC), who didn’t have an ALK translocation or EGFR mutation, sought to answer the question of whether the anti-PD–1 checkpoint inhibitor pembrolizumab (Keytruda) would be better than chemotherapy in patients whose tumours had an expression of PD-L1 between 1–49%.

Readers may recall that pembrolizumab has already received FDA approval for the treatment of first-line NSCLC in patients with greater than 50% PD-L1 expression, based on data for the KEYNOTE–024 trial that was presented back at ESMO 2016 by Dr Martin Reck.

So what’s the verdict? 

Dr Lopes kindly spoke to Biotech Strategy and shared his perspective on the trial data he shared with ASCO. Will the KEYNOTE–042 trial change the standard of care, and how does it fit in with the KEYNOTE–189 trial data that we heard about at the 2018 AACR annual meeting back in April?

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What we wanted to accomplish in our latest thought leader interview was to peek under the hood with someone active in this field who is an experienced participant in phase 2 and 3 trials, as well as being a solid translational researcher capable of thinking outside the box critically.

Stacking up the evidence from IO trials

Today we cover a global KOL’s perspectives on cancers of the lung, renal, bladder, and even melanoma, in a wide ranging discussion about immunotherapy trials and some of the pitfalls and opportunities to watch out for.

It makes for an intriguing read as there are likely a few issues that many have not thought about in great depth.

This is an important discussion in the context of not just data that was recently presented at several conferences including AACR, but also with the upcoming monotherapy and chemo combination trials (including squamous and non-squamous lung cancer) expected at ASCO in a few weeks time.

We discuss quite a few of the key challenges and opportunities relating to the broader picture and highlight some of the important issues to watch out for…

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At AACR last week we had the long awaited initial readouts for three key phase 3 studies in lung cancer, namely CheckMate–227, IMpower150, and KEYNOTE–189 in the same session on the same day.

This had me thinking about how it might end up being, “a killer and a chiller and a thriller when I get the (PD–1) gorilla in Manila,” with sincere apologies to Muhammed Ali and Dr Jean-Charles Soria for (mis)appropriating their past themes 😉

Chicago River Bridge at #AACR18

For those attending the event, you might well be forgiven for thinking from the first two adjectives that I’m referring to the weather, as it was certainly cold enough (!), or even the results this week from AstraZeneca’s unfortunately named ARCTIC study exploring the IO-IO combo of durvalumab plus tremelimumab in the third line setting with a miss in both PFS and OS endpoints.

In reality, we should be warmed and heartened to see three positive immunotheraopy trials appear at once and presented in the same session at the same meeting.  It isn’t always the case as regular attendees at ASCO well know.

When all is said and done, what do thought leaders specialising in lung cancer really think about the data that was presented in Chicago, and what were the convergence and discord on the various key issues under consideration?  There is, after all, a lot of subtlety and nuance to consider in 1L NSCLC.

To find out more, we interviewed not one, but four, lung cancer specialists in Chicago for their personal perspectives.  What they had to say as a group was both candid and absolutely fascinating, so it made sense to curate their insights around various key topics together into one detailed post for easy reading… 

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Chicago!

One of the key topics arising out of probably the hottest session (lung cancer clinical trials plenary) at AACR last week was tumour mutation burden (TMB).

An important question to be addressed was whether or not the nivolumab plus ipilimumab combination from the CheckMate–227 study will be useful in previously untreated non-small cell lung cancer (NSCLC) patients with a high TMB?

There are a number of questions that occurred to us that need careful consideration:

  • Is TMB ready for prime time?
  • What are the challenges and issues involved?
  • How useful are the data from CheckMate–227 and CheckMate–568?
  • Where are we going next?

To find out more, we had some fascination discussions at AACR with two up and coming young researchers from industry (Dr David Fabrizio of Foundation Medicine) and academia (Dr Nicky McGranahan from UCL in London), who are both experts intimately involved in measuring TMB.

What did they had to say and what does it all mean?

Their candid answers may well surprise a few people…

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After yesterday’s notes on the exciting lung cancer clinical trials plenary, I received a bunch of questions from readers following yesterday’s analysis of the 1L NSCLC market.

This is a good opportunity to take some time out to answer some of them, as they highlight some important points worth discussing, clarifying and reviewing.

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At ESMO IO last Fall, Genentech/Roche were first past the post in 1L non-small cell lung cancer (NSCLC) with data from their phase 3 study in non-squamous patients evaluating the combination of chemotherapy and bevacizumab plus atezolizumab versus chemotherapy alone.

The 1L NSCLC race continues apace…

Since then, there has been much anticipatory excitement for BMS and Merck’s phase 3 trials, CheckMate-227 and KEYNOTE189, respectively.  These data will be now presented at the annual meeting of AACR in Chicago next month.

In the meantime, there are also the overall survival data expected soon from AstraZeneca’s MYSTIC trial – will it be positive despite a PFS miss?

Later this year, the company have another study (NEPTUNE) result expected that explores the combination of durvalumab plus tremelimumab versus platinum-based standard chemotherapy in first line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.  This has been a controversial area for IO studies to date and the story here may well be more subtle and complex than many realise.

Next year we can also expect to see more readouts from Pfizer/EMD Serono’s JAVELIN LUNG 100 (avelumab) in both squamous and non-squamous histologies, while AstraZeneca’s POSEIDON study is in squamous patients only.

Just this week, Genentech again announced their phase 3 squamous NSCLC trial readout with positive PFS in favour of the combination of chemotherapy plus atezolizumab versus chemotherapy alone.  The BMS CheckMate-227 study included both sets of histologies and no details were provided in the announcement, so hopefully this data will be available at AACR.

In Pharmaland we hear much noise around First-in-Class and Best-in-Class claims but, ultimately, it will all come down to data.  In oncology, it always does.

In our latest review post, we take a look at both squamous and non-squamous settings and what we learn from the latest available information.  Surprisingly, it’s quite a lot and there are important nuances to consider as well…

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BMS LogoThe big news of interest in the oncology landscape this morning is the BMS announcement that the CheckMate–227 study hit its primary endpoint of PFS under certain conditions in previously untreated non-small cell lung cancer (NSCLC).

We’ve been covering the 1L NSCLC landscape for a while now and this study was one that was less easy to predict than the others for a number of reasons. I’m pleased to say we got it right, although there are quite a few things to learn from this announcement, not to mention some important implications too.

Here, we continue our coverage on this topic with an analysis based on the latest information…

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After writing about the 1L NSCLC landscape every quarter last year, I was thinking the other day that we were due another update and discussion on this riveting topic again soon and added it to the editorial calendar of topics to write about on BSB.

It was therefore no surprise to hear Merck’s announcement this morning that their phase 3 trial KEYNOTE-189 exploring pembrolizumab plus chemotherapy hit its co-primary endpoints and is now the second study to do so after Genentech/Roche’s announcement for atezolizumab plus chemo plus the VEGF inhibitor, bevacizumab was a success.

Are we at a crossroad for lung cancer?  With many more readouts yet to come competition in this space is certainly heating up dramatically!

Meanwhile, there are a few important implications to consider here, so we sat down and penned an update based on the emerging data and highlight some key insights to consider…

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Periodically, we post an analysis and look at a particular landscape and the leading competitors within. One area of rather intense interest that we have been following is the progress (or march might be more precise) of checkpoint blockade in previously untreated metastatic non-small cell lung cancer (1L NSCLC).

Our extensive reviews and discussions in this area have included a look at:

In addition, I last posted my recent predictions on this space in July this year and already quite a bit has happened since then!

With a bunch of other phase 3 trial readouts coming up over the next couple of months, it’s now time for another update on what to watch out for, what to expect and why some studies can be handicapped differently.

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