The calm before the storm as the KRAS competition heats up and also gets more complex in the process
I was very tempted to tease everyone and say something along the lines of… ‘while you were all partying, there was some new KRAS clinical data being presented somewhere in the world’ but that would be rather naughty, I suspect.
Instead, I’ll simply point out that it’s time to take a look at the latest phase 1 data in the KRAS niche.
What more clinical data already?!
Yes there is and what’s more it doesn’t belong to the either of the leading two in the early race to market, aka Amgen and Mirati. There’s a whole bigger world out there for those interested in following the broader slate runners and riders. It pays to pay attention because this is not a race about single agent therapies, rather it’s about who figures out the optimal combinations and is able to finesse that better than their competitors. Like real horse races, an unexpected runner can surprise a few folks by making a strong push on the rails or a bounding leap round the outside like Lester Piggott was famous for doing.
This highly specialised field is moving much faster than the BRAFV600E arena was a decade ago and there’s also more players involved too, plus multiple different approaches and targets to consider, which I expect we will be covering quite a few times during 2020.
Are you ready?
Get set, GO!
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In Pharmaland it is frequently the case that once a target has been validated there’s always new developments in the form of novel agents that emerge, as well as emerging new related targets to consider.
Standing from the KRAS crowd
Here we combine an update on some new market entrants in the KRAS niche with an expert interview discussing how to address a known area of acquired resistance that has recently been highlighted. Naturally, that also brings with it yet more novel targets and potential combination strategies that may need to be considered by players in this space.
Yes, KRAS G12C is now a rapidly evolving area with multiple players and many moving parts, whereas even just back in January this year many observers saw it as a three horse race – think again, it’s much deeper and broader than that somewhat naive hypothesis already!
As usual, we follow these races longitudinally with regular updates and explain why new scientific findings need to be considered if we are to make a difference in the clinic with future combination strategies.
Are you ready for the latest game of 3D chess?
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Boston – One of the most enjoyable things about writing about science and early clinical oncology data is the relationships we build with thought leaders, such that they can be open and honest about their reactions, without them being judged, misinterpreted, or misquoted. We’re on a journey with them, whatever the ups and downs might bring, in a bid to capture the realities of the oncology R&D rollercoaster.
Don’t be fooled by the gloomy Boston weather as a metaphor for data presented at Targets19!
Each story becomes a snapshot in time, a short of ‘Kodak moment’, if you will.
Imagine then, capturing a discussion with a global lung thought leader discussing the initial data from the first-in-man trial with a KRASG12C inhibitor from Mirati (MRTX849) and his experiences in treating people with advanced lung cancer who have the dreaded KRAS mutation, which until recently there were no effective options for.
Thus, we captured the exuberance of seeing objective responses in patients for the first time, “It’s fantastic!” and at the same time qualifying that with a balanced and candidly objective perspective, “it’s still early days.”
Both are true, and not mutually exclusive.
In between these two extremes there is much to think about including understanding the inevitable resistance mechanisms that evolve (primary and secondary), figuring out how to optimize the combination trials as well as reactions to other, seemingly competitive, developments. Our expert in the hot seat today had some rather thought provoking ideas on these important topics to discuss that we wanted to share and stimulate some debate on.
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Barcelona – Today is going to be a very long and complex day at ESMO, with a multitude of key data expected from several trials ranging from the phase 1 Amgen data update on their KRASG12C inhibitor, AMG 510, AstraZeneca’s osimertinib in the FLAURA study plus a raft of others, including the phase 3 PAOLA–1 and CheckMate–227 trials.
In order to keep all the information straight and manage the various embargo deadlines at wildly different times, we’re going to break with tradition and post three different articles at different times on KRAS, FLAURA, and the daily running log of various studies and posters that catch our interest. Yes it’s a lot more work, but it’s the only way to manage all the deadlines!
This post will focus solely for the KRAS updates at ESMO19, including the initial data release, the presentation, analyses, and commentary. No doubt that means a series of updates will ensue so do check back regularly or follow the alerts on Twitter via @biotechstrategy.
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Chariots of Fire in Barcelona?
Barcelona – Gosh, what a weekend chock full of lung cancer data at the World Congress on Lung Cancer hosted by the IASLC!
There’s nothing like a bit of controversy to get riled up or crash with disappointed hopes under the weight of expectation, but if we go under the hood and look carefully, what do we find?
There was a lot of topics that we’re going to cover the important highlights and learnings in a two parter series – today we focus on KRAS with targeted therapy, while tomorrow we look at other topics of interest, both targeted and immunologic.
Without much ado, let’s roll with the Amgen update as there are many subtleties and nuances to consider…
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