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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One of the obvious learnings from the American Association of Clinical Research (AACR) meeting earlier this week was that we are coming to the end of the low hanging fruit opportunities for checkpoint inhibitors as monotherapies.
Speaking with numerous company people in this space, there was wide consensus on that point. As one clinical lead put it succinctly, “From here on out, it’s going to get way more complicated – had a low grade headache develop after the very first science session I attended – and it’s still there after two days!”
How many of us know that feeling all too well? AACR always has the heaviest science load of any cancer conference we attend each year. Sure there’s some nice clinical data, but that is like nibbling on the light appetizers before the 20 course banquet. You need much stamina and fortitude to survive the brain fog at AACR. Then there’s the glee at snagging some key poster handouts at the meeting, only to be rapidly diminished when you try to read the 4pt print post hoc and realise your eyes cannot focus easily.
Looking at the long list of topics I want to cover in the in-depth post meeting analysis for a ‘lighter’ post, especially given that it’s Friday after a very long week, that sinking feeling hit home hard – there are no lightweight topics at AACR.
The other day, we posted about the promising data in triple negative breast cancer (TNBC), following on from the Genentech and Merck presentations at the San Antonio Breast Cancer Symposium (SABCS). These data surprised many folks, mostly because they didn’t consider breast cancer to be an immunogenic tumour – nor is lung cancer in the broader scheme of things for that matter – yet we are seeing some nice durable responses in both tumour types with checkpoint inhibitors.
In other words, our definition and perceptions must change as we redefine how we identify and think of possible ‘responsive’ cancers to these agents.
So where are likely heading next?
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Quick Reminder: Today is the last day for the AACR Special – the discount ends at midnight ET tonight. We may not offer this rate again as it’s a limited time only deal!
With the news hot off the press at the 2015 annual meeting of the American Association for Cancer Research (AACR) that Merck’s pembrolizumab (Keytruda) beat out BMS’s ipilimumab (Yervoy) in advanced melanoma, quite a few readers wrote in asking whether this signals the end for ipilimumab?
The short answer is no, and here’s why…
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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.
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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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