Florence, Italy: Today at the EACR-AACR-SIC Conference on “The Challenges of Optimizing Immuno and Targeted Therapies,” Tom Powles MRCP MD, Clinical Professor of Geniturinary Oncology at Barts Cancer Institute in London, gave a special lecture on the IMvigor211 trial (NCT02302807).
This was a phase 3 study of the PD-L1 checkpoint inhibitor atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer.
Prof Tom Powles (Barts Cancer Institute)
Readers may recall we interviewed Prof Powles back in August 2015 about the potential for the PD-L1 checkpoint inhibitor atezolizumab in urothelial bladder cancer? (See post: Atezolizumab PD-L1 Checkpoint Inhibitor will Change Bladder Cancer Treatment.)
We also featured the atezo data presented by Dr Jonathan Rosenberg (MSKCC) at ESMO 2015 on Episode 7 of the Novel Targets Podcast, where we also heard Prof Powles tell us about the long durable responses he had obtained in clinical practice in some of his patients.
Subsequently on May 18, 2016 the US Food and Drug administration (FDA) granted accelerated approval to atezolizumab (Tecentriq) for urothelial bladder cancer (link to news release).
Fast forward a year to May 9, 2017 and the surprise announcement that the confirmatory phase 3 trial (IMvigor211) failed to meet its primary endpoint (link to Genentech press release).
So what happened? Why did the atezo phase 3 trial end up being negative when we saw durable responses in the randomised phase 2 trial and other PD-1 checkpoint inhibitors have shown an overall survival benefit in the same indication?
Many in the media only want to write about positive data, but in science we often learn as much from our failures as we do from our successes, perhaps even more sometimes.
IMvigor211 was expected to be a positive trial especially after the recent Merck success gaining an overall survival benefit for pembrolizumab, so the negative result is noteworthy and one that anyone in the field of cancer immunotherapy drug development will want to understand.
Professor Powles kindly spoke to BSB and shared his perspective.
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Cambridge: the third annual European Association for Cancer Research (EACR) conference on cancer genomics is underway at Churchill College in the UK. (Official Twitter hashtag: #CG17).
Churchill College, founded by the former Prime Minister, Sir Winston Churchill, is a short 15 minutes walk from the historic city centre and has an edgy modernist field to it, with thought provoking sculptures scattered throughout the grounds. It’s a far cry from the more romantic and dreamy spires of Oxford portrayed in the TV detective series, Morse and Lewis.
Despite all the interest in cancer immunotherapy and immuno-oncology, it’s important to remember that cancer remains a disease of the genome, which is why we decided to cover this meeting for the first time. It has an impressive line-up of keynote speakers, as well as researchers presenting posters.
All too often now on the cancer immunotherapy conference circuit, it’s the same thought leaders giving a repeat of their ‘party piece’ standard “keynote” talk so it’s refreshing to hear new voices who are at the leading edge of cancer research, albeit in a slightly different niche.
What we are starting to see is the convergence of cancer immunotherapy with genomics, and that was very evident in the posters that are directional of where the field is going. More on that later.
This is the first of three daily blogs that summarise some of the insights and take-home messages from the EACR Cancer Genomics conference at Churchill College, Cambridge.
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One of my favourite pastimes at cancer conferences is discussions with up and coming young researchers about their current experiments and what they learn from them.
The poster hall rugby scrum at #ASCO17
In the spotlight today is one of the gems from the poster halls at ASCO this month…
Here we explore how liver mets, which is a common site of metastases, can influence the response of cancer immunotherapy.
The findings from this research highlight some intriguing biology as well as offer some hints about where to go next.
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Yesterday, we had a sarcoma expert in the spotlight looking at the new developments from the American Society of Clinical Oncology (ASCO).
In part two of our sarcoma mini-series, we have another interview for our readers, this time from the perspective of the CEO, Dr Carlos Paya. They had some interesting data in Chicago so what was their reaction to it and where are they going next?
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Sarcomas are a heterogeneous type of cancer that develop from certain tissues like bone or soft tissues such fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.
Over the last two years, much has happened in this space so it’s an excellent time to revisit the niche and learn more about what experts think of the latest data that is emerging here.
We put a sarcoma expert in the spotlight and learned what their perspectives are on some of the emerging data in this niche as well as which ones offer hints of promise.
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As we start to see early readouts from new IO combos and also new trials emerge to begin enrolling patients, it’s going to be intriguing to see how the new cancer immunotherapy landscape evolves.
Some of these trials will be random in that the drugs are what the company has, others will be based on existing or new collaborations, while others will be based on rationally based science… not all will be successful, though.
Of course, it’s easy for all of us to be an armchair critic and grumble about the flaws, the problems, and even the weaknesses in clinical trials, but what about rational approaches that attempt to scientifically address the acquired resistance that develops on montherapies?
Here’s one approach I really like – we’ve written about the underlying biology behind it previously, but what about the clinical trials, and what does the company evaluating the combos think?
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There’s nothing like a bit of controversy and heated debate at the annual meeting of the American Society of Clinical Oncology (ASCO) – every year seems to have something of note that generates intense debate and this June was no exception.
The main focus of this year’s intrigue was the APHINITY trial where pertuzumab (Perjeta) was added to the standard of care treatment – trastuzumab (Herceptin) plus chemotherapy for one year – in HER2+ adjuvant breast cancer.
The reality is that the findings from this trial are both subtle and nuanced so what did thought leaders really think about the data – what does the magnitude of the benefit mean and for whom should we be considering this approach for?
To find out, in the fourth post in our breast cancer series we interviewed some experts and curated sentiments around APHINITY to determine what the consensus was and where things are going next.
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#ASCO17 Poster Hall aka rugby scrum
There were a lot of gems in the poster halls at ASCO this year, a fact that is partly a reflection of the wealth of new data with various IO combos and also the early cutoff date.
Now I jested before the meeting that these sessions were akin to a rugby scrum and lo and behold (see photo right) they were even more jam packed than usual!
If you wanted to best the eager and energetic Wall St analysts then remembering your ruck and maul skills were not a bad thing to have in muscle memory… It was not something I attempted in the Go-Cart this year for fear of bowling people over in the stampede to nab the QR codes 🙂
Much of the previous readouts have been with monotherapy in immunogenic tumours such as melanoma, lung, bladder, gastric, renal cell carcinoma etc. Objective response rates in metastatic triple negative breast cancer (TNBC) have generally been under 20%, however.
Lately, the focus has turned to the deepening of responses in these tumours with various combination approaches and also moving earlier in the disease setting, where immunotherapies might be expected to be more effective with a lower tumour burden.
While in Chicago, we spoke to a breast cancer specialist about where IO combos are going and his thoughts on future opportunities in our third post in a series on various aspects of new developments in breast cancer.
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It amuses me to realise that I’ve been writing about and following PARP inhibition since 2006 or so, when the field was in that twilight zone of early drug development between preclinical and clinical, thus just beginning to hit some sort of consciousness and broader interest in cancer research.
The AACR Molecular Targets meeting in 2009 was the first scientific meeting I covered as a science writer on the old Pharma Strategy Blog, which focused on early drug development from preclinical to phase 2 – after that I would rapidly lose interest and move on to the next new shiny scientific lure to research and discuss. No doubt this eager new writer ran about like an overenthusiastic little puppy in the poster halls chatting to scientists about their research, much to the amusement of the more staid press room, who at that time probably never ventured out of the darkened basement gloom.
In one of the press briefings there, I met an engaging and thoughtful scientist who was presenting his poster on PARP and synthetic lethality. He kindly took the time to explain in plain English a commonsense analogy that was most helpful for grasping complex concepts. Having sat through several long talks from luminaries in the field such as Drs Hillary Calvert and Alan Ashworth that covered double strand breaks and DNA repair mechanisms, it was a most welcome respite in the hurly burly of the conference!
Imagine his imagery…
You have a four legged coffee table or wooden chair and one of the legs breaks off or is damaged. The table remains standing, albeit less stable than before. Now a second leg breaks, and inevitably, the table is so unstable that it falls over.
Once you grasp that simple analogy for synthetic lethality, you have the basic idea of DNA double strand breaks and how inefficient repair can lead to vulnerabilities in the tumour that can be exploited.
The scientist I spoke to in Boston back in 2009 was Dr Mark O’Connor.
He was involved in DNA damage response research at a little known private company in Cambridge, UK called KuDos, who were subsequently acquired by AstraZeneca. Nearly a decade on and Dr O’Connor is still at the company; he now heads up their DNA damage response area.
Dr Mark O’Connor, AZN
With olaparib (Lynparza) since approved by the FDA in ovarian cancer and slated for the ASCO 2017 plenary session for HER2- breast cancer, things have certainly changed a lot since those early heady days of KuDos and the R&D journey has not been without its notable ups and downs along the way.
In Chicago earlier this month, I had the pleasure of catching up again with Dr O’Connor to learn more about the journey, and importantly, where things are going next. It’s quite an interesting roller coaster ride, to be sure!
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Often times when we see promising data presented at a cancer conference, we interview a thought leader and post the expert opinion with additional commentary and insights.
ASCO17 OlympiAD Plenary
At ASCO, we decided to take a different approach, a twist on the usual fare… given that two of the phase 3 trials, OLYMPIAD and APHINITY, received significant attention and focus involved breast cancer, we reached out to numerous experts and curated their sentiments on both studies. For completeness and fair balance, these included industry and academic opinions.
Today, we begin with the OLYMPIAD trial presented by Dr Mark Robson on behalf of his colleagues exploring the role of the PARP inhibitor, olaparib (Lynparaza), in HER2-negative metastatic breast cancer with germline BRCA mutations.
There’s a lot to consider here, not least is where do we go next from here and which PARP combination approaches are researchers most excited about?
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