BioTwitter is all a-flutter today with the announcement from BMS that the CheckMate–026 trial in first line non-small cell lung cancer (NSCLC) comparing nivolumab (Opdivo) to chemotherapy did NOT meet its primary endpoint of progression-free survival (PFS).
The news was not entirely a surprise to us at BSB, here’s why…
Figurative statute representing Science on Holborn Viaduct in City of London.
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One of the hotly debated topics at the 2014 American Society of Hematology (ASH) annual meeting was the arrival of checkpoint data in classical Hodgkin’s lymphoma (cHL), with initial data presented on 20-30 patients with relapsed or refractory cHL who received either nivolumab (BMS) or pembrolizumab (Merck) in open label, single agent trials.
Updated phase I data is expected to be presented at the 2015 ASH annual meeting in Orlando (Dec 5-8) (Twitter #ASH15)
At the recent ESMO symposium on Immuno-Oncology in Lausanne (Twitter #Immuno15) – great hashtag, there was an excellent overview of checkpoint blockade in lymphomas. What did this tell us about progress in this disease and where are things going?
The ESMO IO meeting set the scene for what we can expect at ASH this year?
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Anyone who has been regularly to the American Society of Clinical Oncology (ASCO) over the last decade or two will have have sat through quite a lot of trials with doublets and triplets in numerous advanced solid tumours and seen an impressive graveyard of failed cytotoxics and targeted therapies build up… Too toxic, lack of efficacy, futile even. This is especially true for some of the more difficult to treat cancers such as pancreatic, small cell lung cancer, melanoma, glioblastoma and soft tissue sarcomas.
There is hope though, after all, things have changed quite dramatically in the metastatic melanoma landscape over the last five years that it is now quite unrecognisable compared to a decade or even five years ago. This is very good news indeed.
What about the other tumour types in that list, though? How are we making progress with those?
In the latest series here on BSB, we’re going to focus on the new developments happening on the fringes of cancer research out of the main spotlight and look in more depth at what’s looking promising in some of these areas. Today, we’re going to start with small cell lung cancer (SCLC), a truly devastating disease with a horribly dismal prognosis.
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Much has been written about the success of checkpoint blockade in solid tumours over the last couple of years with the advent of anti-CTLA4 therapy (ipilimumab/Yervoy) for metastatic melanoma followed by the more recent approval of the anti-PD-1 antibodies in advanced melanoma (pembrolizumab/Keytruda and nivolumab/Opdivo) and lung cancer (nivolumab).
What about hematologic malignancies though?
At the recent American Society of Hematology (ASH) conference, we heard about the first clinical data for anti-PD1 antibodies in patients with refractory classic Hodgkins Lymphomas (cHL) and saw some impressive results. Interestingly, though, the early preclinical work was conducted in mice looking at CTLA4 blockade in a variety of tumours, both solid and liquid.
Is there a rationale for targeting CTLA4 in leukemias, lymphomas and even myeloma? New data presented at a medical meeting in patients with heavily pre-treated and relapsed disease post stem cell transplantation suggests that this might be feasible.
Check out to today’s article to learn more about this clinical opportunity in more detail – you can log in or subscribe in the box below.
Over the last few years we’ve heard a lot about the evaluation of predictive biomarkers for checkpoint inhibitors, in particular the value of using PD-L1, whether on immune or tumour cells, as a way of separating responders and non-responders to therapy with anti-PD1 or anti-PDL1 blockers. The results to date have been mixed, with some KOLs concluding that smoking history or number of mutations was more useful in lung cancer and others believing that their assay has better utility.
Some cynical observers I’ve come across have even asserted that companies don’t want to see biomarkers emerge because that then limits their opportunity for patients being treated. Ouch! I don’t believe this to be true, it’s highly complex science and there is much about the healthy immune system that we still don’t know, never mind under more complex situations such as cancer. This is an ever-evolving field about which we still have much learn.
Eventually, we may see further refinement of these approaches, at least in some tumour types and I’m particularly looking forward to hearing more about those advances at ASCO and ASH later this year when the clinical and translational work is more mature.
Next month heralds the annual meeting of the American Association for Cancer Research (AACR). As we noted in our first AACR Preview on Immunotherapy last week, it’s the first time immunotherapy has literally dominated a largely preclinical and scientific program of this nature.
Over the next week or two, will be be highlighting and explaining some of the emerging trends in more detail.
On the important topic of biomarkers, one new approach particularly caught my eye in the abstracts that were released yesterday is worthy of further discussion since it could have important implications to future clinical approaches.
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With all the heightened interest in checkpoint inhibitors of late, I wanted to continue my series on what did we learn from the updated data at ESMO that was different from ASCO? Last week we discussed gastric and bladder cancers, this week it’s the turn of lung cancer, or more specifically, non-small cell lung cancer (NSCLC).
By chance, some interesting announcements have also happened since ESMO with the third quarter earnings calls going on from the main players in this space, which also add colour to the developments in this niche. BMS, for example, announced that they expect their rolling NDA for Opdivo in lung cancer to be completed before the year end and will be presenting the CHECKMATE 063 data this week, while Merck announced their Breakthrough therapy designation for Keytruda in lung cancer this morning.
All in all, this makes the lung cancer space a lot more exciting than it was at ASCO, where the response to the data was fairly muted.
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