Biotech Strategy Blog

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

Posts tagged ‘olaparib’

It’s time to tackle some controversies in advanced prostate cancer and look at exactly who’s pulling a rabbit out of a hat?

At ASCO GU we saw new phase 3 data from the 1L metastatic castrate resistant prostate cancer (mCRPC) setting with very different results produced for olaparib and niraparib, generating quite a bit of debate.

Here we explore half a dozen key issues in the context of both trials and look under the skin at the important subtleties and nuances to think about…

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With two oncology data drops running this week in the ASCO Plenary session plus the GU sympoisum, it’s time to switch our attention from cell therapy novelties to new developments in targeted therapies.

In this discussion, we take a look at an important phase 3 trial readout being presented this week in metastatic castration resistant prostate cancer (mCRPC).

For far too long the GU oncologist’s choices were pretty much limited to androgen receptor (AR) antagonists such as enzalutamide and abiraterone and chemotherapy (docetaxel and cabazitaxel).

Then along came PARP inhibitors such as olaparib, rucaparib, and more recently niraparib, largely limited to men with homologous recombination repair deficiencies who had received prior therapy, with the first two receiving full or accelerated approval in first half of 2020 on the basis of the PROfound and TRITON2 studies, respectively.

The third PARPi is further behind the others, finally just publishing their phase 2 monotherapy data from GALAHAD earlier this month.

Now there’s a new phase 3 data readout to explore and consider in the context of earlier in the disease setting…

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There are at seemingly endless genes associated with genomic instability and the development of cancer – there are at least 450 genes associated with DNA Damage Repair (DDR) alone, for example.

This means it is, perhaps, not at all surprising these can not only induce significant changes in various tumours, but they also might have deeper interactions between them as well, many of which we may not yet know about.

Just as we have seen some success with PARP inhibitors in patients with BRCA loss of function, so too are companies seeking to exploit additional vulnerabilities by targeting the achilles heel with other paired approaches such as ATR inhibitors in cancers where there is ATM loss of function.

There has been a raft of data in this niche from several agents in this class so it’s time to turn our attention to reviewing what we learned from the many subtleties and nuances that inevitably abound in this DDR subniche, including recent data presented by Repare Therapeutics at the AACR-NCI-EORTC meeting…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season for our ongoing TRIPLE meeting coverage – you can either log-in or click to access our latest analysis.

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Where are we headed in the DDR niche?

The dog days of summer always seem to portend a mix of sunny days and stormy skies ahead…

In this latest report we cover important issues around homologous repair deficiency (HRD), new replication stress targets, as well as how both analysis and assays are being developed to meet the evolving needs of the field.

There is much nuance going on behind the scenes, which will be important to keep up to date with, including some tumour types not previously associated with DNA damage repair, something we highlight in this post.

These findings might have implications for future regimens and may explain some of the undetected mechanisms of resistance we are seeing in existing trials being presented at ESMO or the forthcoming Molecular Targets (TRIPLE) meeting.

There are also diagnostic developments to think about, not just therapeutic ones…

BSB subscribers can read more on our latest update regarding HRD and DDR inhibitors, plus our latest expert interview from ASCO – you can log-in or click to access the new content.

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Source: Wikipedia

We first wrote about the fascinating and complex space way of synthetic lethality and PARP inhibition way back in 2006 when the early preclinical developments and targets were just emerging and finally here we are – 15 years later – with the very first phase 3 data in the adjuvant setting.

It’s not often I get to highlight someone and their extensive research from my alma mater, but it’s a delightful opportunity to put it on the front page for a change. The gritty urban setting is a far cry from the romance of the other Kings College (in Cambridge), although the two cities do overlap somewhat in this particular story.

What can we learn from the latest clinical development in early stage breast cancer and what don’t we yet know?

There’s actually quite a lot to ponder and digest here…

BSB subscribers can read more on our initial perspectives regarding PARP inhibition in early stage breast cancer and the OlympiA trial, subscribers can log-in or you can click to read our ASCO21 coverage.

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Every year the sweet spot sandwiched between AACR and ASCO comes around all to quickly, as we’re wrapping up interviews conducted at one and preparing the previews for the other, never mind ESMO Breast, AAI, and ASGCT all coming in May as well.

Cambridge Botanical Gardens

This year is no different and I’m delighted to say they segue rather nicely for once!

It’s hard to believe we’ve been writing about DNA damage repair and PARP inhibitors since 2008/2009 or so, and still this topic just keeps growing and growing!

We’ve certainly come a long way since those early days and now the broader DDR niche is also expanding as more targets are identified and evaluated, both in animal models as well as the clinic.

This list will also increase as CRISPR screens continue to identify synthetically lethal targets – some will be useful, others will fall by the wayside due to lack of efficacy or poor tolerability. Finding a balance between the two will therefore be a big key to success.

In this post we’re going to start with an update on the PARP1/2 inhibitors then catch up on data from other DDR family targets and finally explore a pipeline discussion with an industry expert who is well versed in the DDR field.

To learn more about our ongoing post AACR21 and pre ASCO meeting analysis and expert interviews to get a heads up on key oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Imagine the DDR pathway as a mass of many different notes and targets all interconnected…

We’re on our fifth AACR Preview already this year and there’s plenty more science and clinical topics to cover yet as we go through the emerging topics up on deck.

In this latest update we take a look at the growing field of DNA damage repair – not just old targets, but a raft of emerging ones too, some of which are still in early preclinical development while others are in early phase 1 trials.

We also have some expert commentary on some of these new targets – what stands out, what’s validated and just as importantly, what’s not?

It’s time to get to the centre of things in PARP-land…

To learn more about the hot topics at AACR21 and get a heads up on our oncology commentary and insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

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One thing I really miss from attending live conferences – aside from catching up with people in person – is “the living like a local” experience. Last time I was in Madrid, for example, there was this fishmonger (pescaderia) just a block down from the rented apartment. They were only open in the mornings, so you could dash down the hill, quickly nab some fresh produce, refrigerate it and have something nice to look forward to for dinner with a glass of wine at the end of a tiring day while writing up the highlights…

The image also offers another analogy – do some data presented at a meeting end up, well, a bit fishy on closer examination or reflection despite much of the hype enthused or extolled by others?

At the ESMO20 virtual Congress, we covered a tremendous amount of details from the data during both the daily highlights as well as the previews exploring what to watch out in the run-up to the event.  You can find all those reviews here.

There are always some surprises in store, however, both good and bad.  There’s also layers of obfuscation going on to consider in the form of cheerleading from companies, investigators, or stock holders, which may add positive spin on what is essentially so-so data, cases where great data goes largely ignored for whatever reason, or important lessons to be learned from failure.

In this wrap-up post, we take a sharp look at the ESMO20 winners, losers, and risers from a contrarian’s perspective…

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to ESMO20 virtual congress, subscribers can log-in or you can click to gain access to BSB Premium Content.

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A typical scene from ESMO 2019

Not in Madrid – Is it really only a year ago many of us were frantically dashing around at ESMO last year navigating crowded corridors, long queues for coffee, hunting down the last empty seat in jam packed halls, not to mention feeling the anticipation build for key data being presented in the Presidential sessions?

There are undoubtedly many advantages to virtual digital meetings, aside from the broader access for more people it provides and being able to see the slides unimpeded, yet it must be confessed the things I miss the most are the social interactions and catching up with people and their lives, however brief a moment it may be amongst the hurly burly of 20,000 other souls.

The cultural things we take for granted are often the very essence of what we miss most when they’re no longer obtainable.

Who truly would have guessed our world could be completely upended by the unexpected events of a global pandemic since then? In some ways, it has changed our perception of both time and space.

We have also seen some surprising changes in the fortunes of various clinical trials; some completely rational and predictable, others quite the opposite, as we learned yesterday in a very topsy turvy kind of way.

It’s time to discuss and review the highlights – and lowlights – from ESMO20 Sunday in part 2 of our daily coverage…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Not in Madrid: The 2020 virtual congress of the European Society for Medical Oncology (#ESMO20) is underway and in this post we’re taking a look at some of the highlights from Friday at ESMO20, a day when we’ve seen a raft of posters and mini-orals released for on-demand viewing.

ESMO20 BannerWith COVID-19 rates rising across Europe, ESMO are to be congratulated for pivoting to a virtual meeting that allows the sharing of knowledge and advancement of the field. It was definitely the right decision in light of the ongoing travel challenges, quarantines, not to mention restrictions on large groups in many countries.

For our daily ESMO20 coverage – just as we would if we had been in Madrid – we’ve been listening to some of the on-demand mini-oral presentations and associated discussions, with a view to picking out and commenting on a few that stood out for us.

As always we’re approaching this from a cancer new product development perspective, and our choice is always a balance of emerging new targets and drugs, as well as following those we’ve previously written about.

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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