Rodin’s The Thinker sculpture Source: Wikimedia Commons
Recently, I have been pondering a raft of clinical and translational data we have seen emerge across multiple virtual conferences from several different categories of therapies such as checkpoint blockade, targeted therapies, PARP inhibition, epigenetics, and even mathematics.
Many people tend to look at these disparate categories and see them as quite different therapeutic options, but lately I have began to wonder if they are in fact much more inextricably linked than seems obvious at first glance?
This turned into a broader strategic post about advanced solid tumours and how we might think a little differently about underlying concepts and conceptual frameworks…
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This last week saw the ASCO Breast Cancer Symposium in San Francisco, although very little caught my attention from a drug development point of view. Much of the attention seemed to be focused on surgery, genetic counselling and screening.
With the 2014 European Society of Medical Oncology (ESMO) conference in Madrid coming up fast in only 2 weeks time, it seems a good point to take a look at what’s on the slate there, since there are some important clinical trials being presented there with new data that we can expect to hear a lot more about.
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Companies mentioned: Roche/Genentech, GSK, Novartis, AstraZeneca, Medivation, Astellas
Drugs mentioned: Pertuzumab, trastuzumab, lapatinib, PI3K inhibitors, olaparib, enzalutamide
There are a couple of important breast cancer trials with data being presented for the first time at Madrid.
To round off our series of post AACR reviews this week (there will be more coming next week as well, don’t worry), I wanted to look at some interesting non-immunotherapeutic agents that I found compelling and worth watching out for in the future.
A couple of things to remember or understand is that AACR is a very different conference from ASH and ASCO, aside from the presence of noticeably more science:
a) Much of the data presented at this meeting is either preclinical or phase I-II cinical data
b) Most of these studies are usually exploratory or preliminary in nature
Phase I trials are usually designed to evaluate dose finding in either a single agent or with an untested and untried combination. Investigators are interested in a number of key things here, which might include:
- Maximum tolerated dose (MTD)
- Dose limiting toxicities (DLT)
- A recomemmended phase II dose (RP2D)
- PK and PD
- General tolerability assessment.
Sometimes a different formulation is tested, in which case bioavailabity is also important. To be expressly clear though – any efficacy signals seen are a bonus. That’s the main purpose of phase II trials.
That said, one of the things I most like about AACR is the early phase I data in new targets or data that explains why resistance develops as an adaptive response to therapy. With these in mind, here are three excellent examples from well put together research from the meeting that we can learn a lot from.
To read more about our analysis of up and coming compounds including:
DEDN6526A, a novel ADC in melanoma; AG–221 in IDH2 mutant AML and MDS; a PI3K-α isomer-specific inhitor, BYL719, and the impact of PTEN alterations
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