Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Churchill College, Cambridge: Yesterday heralded the 4th and final day of the EACR Cancer Genomics conference with some invited speakers and proffered papers based on research from several groups and labs.

Churchill College, Cambridge

We got to see through the keyhole on several important areas of research that highlight both challenges and opportunities faced by the field.

The good news is that the opportunities provide insights into how we can learn from ongoing and optimise future clinical trials.

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Churchill College, Cambridge:  Yesterday, the main focus at the EACR Cancer Genomics conference was on immunology-related topics as they pertain to genomics.

A rainy day in the Fens for #CG17

Unfortunately, however, the Great British summer ended as almost as soon as it started – I can confirm that it started on a Wednesday this year and fizzled out by the following Tuesday!

Consider that on the first two days of the conference it was gloriously sunny and those wooden benches were full of scientists sitting outside eagerly discussing their research or various collaborations afoot.

A mere 24 hours later, the heavens opened and steadfastly drizzled all day long, much to the chagrin of the attendees.

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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).

EACR AACR SIC Conf Banner

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)

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.

ASCO17

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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