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

Posts tagged ‘AACR 2018 Chicago’

AACR18 Day 2 Highlights

The lull before the Monday storm hits…

One of the highlights every year at the annual meeting of the American Association for Cancer Research (AACR) for me is catching up on new product development and finding out which molecules are moving along and which have encountered unexpected issues and most importantly, why. Drug development is an inexact science, after all, and sometimes it is more akin to art.

Sometimes you hear of a promising new or very early molecule in these sessions and follow them all the way to the market, while other times they get touted as such and then flame and burn out later.  Some years are also better than others, for obvious reasons.

How did 2018 turn out?  What’s to watch out for this time around?  A couple of years ago we had a dismal session here with the majority of agents clearly destined to the scrapheap and the poor researcher was dutifully performing the office of last rites. This year I’m pleased to say was quite different and there was much to be encouraged by…

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AACR18: Day 1 Cancer & Immunology Symposium

We often talk about ‘on-target off-target’ side effects, but what about the equivalent on-site off-the-reservation meetings?  I’m a big fan of these, it has to be said.

Spring time in Chicago feels more like… October – brrrr!

My first day at AACR18 in Chicago this year was sandwiched by two such events, one of those welcome to AACR moments – never mind the frigid weather – to be sure.

First off, you have to be on the relevant distribution lists to get invited, then hope the organisers accept your registration, such is the life of scientists on the dark side (journalism/media).

In the past, these off-reservation scientific events around AACR have been well run and very useful for picking up new companies or targets ahead of the mainstream news and this year I wasn’t disappointed.

One of the Previews that I didn’t get time to write up was on CAR T cell therapies because there was a huge surfeit of new companies, new targets and lots of unproven mouse data, which is a recipe for speculation without representation (of clinical data).  So on the basis that the good stuff will rise to the top, I figured that it might be more efficient to summarise an event instead, as past events have proven very useful in this somewhat singular approach.

We all know that we need to go beyond CD19 as a target in hematology malignancies, and that the promise in solid tumours is high, but data scant, so where are the gems to watch out for?

Here. we take a look at some up-and-coming approaches and companies to watch out for to cut to the chase for BSB readers interested in this space…

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An under-appreciated oncology drug class

The convergence between targeted therapies and immunotherapies with genomics has already started in many areas of cancer research – we can imagine the intersections more as a Venn diagram than as separate entities these days.

Lobster pots on the shore

While former graveyards of R&D such as metastatic melanoma and lung cancer have seen a dramatic revival in positive trials over the last five years, things have languished somewhat in other areas.

Womens cancers such as high grade serous ovarian cancer (HGSOC) and triple negative breast cancer (TNBC) have seen some new developments with the advent of PARP inhibitors as monotherapy or maintenance, but there is still a ways to go in terms of overcoming resistance and improving outcomes further.

You might be puzzled what on earth lobster pots have to do with cancer research? In short it’s an apt analogy from life because while there is much promise in the right situation (under the sea in a good situation), they can also look like a helpless mess (abandoned on the shore).  Oncology R&D is a bit like that too and finding the right situation viz molecule development and clinical trial design, not to mention discontinuation is very similar in that respect too.

In our latest AACR18 Preview, we take a look at an underappreciated oncology drug class and look at the opportunities for future combinations that may take a few readers by surprise…

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AACR18 Preview 6: Beyond epacadostat and a look at early IO-IO combinations

Through the window of oncology R&D

With the sad and very gloomy news that Incyte’s IDO inhibitor, epacadostat, has missed in the phase 3 ECHO–301 study in metastatic melanoma, is there still hope for IO-IO combinations in the pipeline?

Here, we take a quick look at the Incyte announcement briefly, but more importantly, we also look forward to other combinations that might be of interest to those following the cancer immunotherapy space.

Not surprisingly, there is a lot to look out for as our sixth post in the AACR18 Preview series highlights as we look through the IO window to potential future developments of interest.

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AACR18 Preview 5: is TGFβ an emerging cancer target?

Finding patterns in the mosaic of cancer biology

In our fifth AACR preview of the annual meeting of 2018, we switch directions from a tumour type to explore a novel and emerging pathway of interest.

Each year we pick a different target to explore; this year it’s the turn of TGFβ.

There’s a lot going on here, both preclinically and clinically that should interest BSB readers who are keen to see new developments in the IO landscape.

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AACR18 Preview 4: a look at new developments in a key tumour type

As part of our annual AACR Preview series, we usually explore new developments in at least one tumour type and one new target of interest.

Bladder cancer cells infected with BCG Source: Dr M Glickman, MSK

This year is no different and there were plenty of opportunities to discuss.

We have already covered lung cancer given the intensive interest in the phase 3 trials being presented in the 1L setting, but I also wanted to cover another key tumour type that is generating a lot of keen interest in clinical development for numerous reasons.

Tomorrow we will be exploring a cancer target in detail, but there is much to cover in terms of new preclinical and clinical developments in certain carcinomas.

Without much ado about nothing since there is plenty of important things to discuss, so here’s a look at our second tumour type to watch out for given the sheer numbers of trials, including a variety of different targets to think about.

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Is there a silver lining in SCLC?

Last October I posted two updates on small cell lung cancer (SCLC). One explored the broad SCLC landscape, while the second was a detailed analysis highlighting the red and green flags to watch out for in the Rova-T TRINITY study.

My sombre conclusion or prediction, if you will, was not particularly well received at that time:

“My sense is that the median PFS and OS in the allcomer ITT population will remain modest and in line with what we might expect from historical chemos in 3L SCLC.”

Dismal happenings are to be expected…

This morning AbbVie announced that they will not be filing for accelerated approval of Rova-T in 3L SCLC based on the interim analysis.  In other words my expectations for this trial were met, although there are many who will be very disappointed at the results.

What matters though is not just how disappointing topline results might be per se, but why they occurred, what we can do about it, and most importantly, where we go next.  There’s a lot more to this than might initially be obvious from the press release.

That’s what this new post is all about… first a post mortem, then the obstacles to be addressed, and finally, what we can look forward to in SCLC…

On a happier note: there may be some surprises ahead!

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The squamous and non-squamous lung cancer race continues!

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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