Biotech Strategy Blog

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

Posts from the ‘Cancer’ category

San Francisco

The first cancer conference of 2018 is now upon us and after enjoying last year’s event in San Francisco, I wanted to take some time to explore some key abstracts of interest at the ASCO GI meeting, which begins tomorrow.

This conference covers various updates on new developments in oesophageal, gastric, colon, pancreatic and colorectal cancers.

Are there any trials or new developments to get excited about at this year’s GI18 meeting?

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After writing about the 1L NSCLC landscape every quarter last year, I was thinking the other day that we were due another update and discussion on this riveting topic again soon and added it to the editorial calendar of topics to write about on BSB.

It was therefore no surprise to hear Merck’s announcement this morning that their phase 3 trial KEYNOTE-189 exploring pembrolizumab plus chemotherapy hit its co-primary endpoints and is now the second study to do so after Genentech/Roche’s announcement for atezolizumab plus chemo plus the VEGF inhibitor, bevacizumab was a success.

Are we at a crossroad for lung cancer?  With many more readouts yet to come competition in this space is certainly heating up dramatically!

Meanwhile, there are a few important implications to consider here, so we sat down and penned an update based on the emerging data and highlight some key insights to consider…

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During the month of January, we’ll be looking at several key themes that will likely have some impact during 2018. This is the first post in the series and each one will entail a different approach.

Ideas from the lab notebook…

We should start to see various ideas begin to overlap across different tumour types. Rather than look at things in isolation, there will be a greater push to explore concepts and how they intersect and come together in a more useful fashion so that a more strategic picture can emerge.

Looking through my lab notebooks from the last 12 months, I decided to highlight some emerging themes that we can expect to see or hear more about during 2018 and came up with a handy list.

Here’s one such example – tomorrow we will take on another topic of interest…

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A short, but quite important, post today highlighting an early target we are keen to follow in terms of combination trials in both GI and GU cancers, as well as others.

There’s been a lot of focus this year on the so-called inflamed (hot) and non-inflamed (cold) tumours, but what about the intermediate ones that many refer to as the immune excluded phenotype?

View of Geneva from Cathedral St Pierre, Switzerland

Clearly it makes sense to consider different combination approaches in each category, but what would be appropriate? Before we can set about doing that, we first have to uncover the mechanisms causing the inhibition on the tumour microenvironment and then figure out how best to identify those patients most likely to benefit.

Over the last couple of years, we’ve seen and written a lot about various potential candidates (not all will be useful), including myeloid derived suppressor cells (MDSCs), regulatory T cells (Tregs), tumour associated macrophages (TAMs), chemokines, cytokines, adenosine fog and many others.

There is one target that has started gathering a little bit steam over the last year that we have mentioned a couple of times on BSB and now there is something new to discuss here, at least from a big picture perspective.

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Geneva: At the ESMO IO 2017 conference underway in Geneva, the data of the meeting is the IMpower150 phase 3 trial data that will be presented later today by Dr Martin Reck (Grosshandsdorf).

Genentech/Roche have announced a press release ahead of the presentation (Link).

This is the first phase 3 lung cancer immunotherapy trial that combines a VEGF inhibitor (bevacizumab/Avastin), along with a PD-L1 checkpoint inhibitor (atezolizumab/Tecentriq) together with chemotherapy (carboplatin plus paclitaxel).

While we’ve not seen the actual data curves yet, we spoke to Dr Dan Chen (Genentech) about what we can expect to see later today in Geneva, and importantly, we also discussed the significance of the findings from the IMpower150 study.

As Dr Chen told BSB, “this trial is a lot of firsts.”

If you have an interest in lung cancer or immunotherapy, do follow #ESMOImmuno17 on Twitter, as this is data could potentially be practice changing and have a major impact on the lung cancer treatment landscape.

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It’s one of those truly crazy busy times of the year with no less than three cancer conferences going on this week alone in different cities and time zones. I’ve also been busy scheduling and conducting phone interviews for these events.  More than once have I dialled the wrong number or access code or got briefly confused by time zone changes (CT and CEST?!) and misread the interview at the wrong time… and was that 4.30pm ET or CT?

River Walk, San Antonio, Texas

One of those… If it’s Tuesday it must be Belgium moments to be sure.

Thankfully, everyone has been very thoughtful and helpful and I haven’t managed to get the expert names incorrect (yet)!

Today, I want to take a break from the ASH17 coverage and switch horses from hematologic malignancies to breast cancer and from Atlanta to San Antonio, as there is some important new data emerging from the Lone Star state.

In particular, one of the top posts of 2016 on BSB was on CDK4/6 inhibitors so it’s time for an update on this and some other key studies!

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Sometimes initial phase 1/1b readouts at cancer conferences produce quite different reactions from a live and remote audience while at other meetings, the Developmental Therapeutics talks produce little or no interest at all. It’s often hard to guage which way they will go.

At SITC this weekend, several talks generated some contentious, and at times quite heated, debate and intense interest.

One of these was an oral presentation by Dr Zev Wainberg on the first-in-man data with the anti-CSF1R and anti-PD1 inhibitors, cabiralizumab and nivolumab, from Five Prime and BMS respectively, in an advanced pancreatic cohort.

Dr Zev Wainberg at SITC 2017

There was a surprising amount of confusion surrounding the initial results and other issues last week, with Five Prime’s stock dropping before we’d even got to Dr Wainberg’s talk.

What became increasingly obvious over the weekend was a clear difference in investors perceptions versus what the scientific community actually thought.

Here we take a look at the data and explain what to watch out for and why…

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SITC 2017

Treatment with checkpoint blockade has undoubtedly improved the lives of some people with advanced cancers such as melanoma and lung cancer, however the number who do achieve complete remission with single agent therapy is low (typically <20%).

In addition, not all people will respond up front while others achieve an objective response then relapse as acquired resistance or immune escape hits.

One challenge facing the field is identifying these mechanisms of resistance and finding the optimal combination approaches that lead to improved outcomes.

This weekend at the Society for Immunotherapy of Cancer (SITC) annual meeting, there were quite a few interesting new combination developments with early data.

Here, we take a look at one such combination to explore the data, the biomarker research that is ongoing and also some of the challenges associated with finding needles in the proverbial haystack…

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We’re at a crossroads in the IO space, where much of the low hanging fruit has been already plucked and now we could be in limbo for the next 2–5 years while we wait to see which of the IO-IO or IO-other combos pan out as winners.

Part of the problem is that we don’t yet know all the potential mechanisms of resistance or immune escape involved, so imagine figuring out how best to optimally modulate the tumour microenvironment on top is going to be challenging – each tumour type is heterogeneous and highly complex.

In addition, the field has heavily skewed towards obsessing almost exclusively over T cells, which may or may not be a good thing.  There are alternative approaches that are starting to generate interest and results.

As Andrew Shepherd, the fictitious leader of the free world in the American President famously said:

“We have serious problems to solve, and we need serious people to solve them.”

One promising company in this space is Nektar Therapeutics.  At SITC this week they had some elegant and intriguing early data that combined an innate immunotherapy approach with checkpoint blockade.  We have been following their progress for a while now and it’s a great time for an update!

Dr Adi Diab NKTR-214 #SITC2017

Here we explore the data and have our latest expert interview that is not merely a couple of paragraphs long with a few platitudes or topline quotes… this is, quite frankly, a comprehensive review and strategic roadmap of what Nektar Therapeutics are doing in the IO space, why they are doing things a certain way, and where they are headed – in their own words…

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National Harbor, MD – Day 2 of #SITC17 brought some interesting highlights on a number of fronts, not all of which may be apparent at present, but there are a few readouts that will have a broader impact going forward.

SITC 2017 Stars?

As we move into an era where we see more combinations evolve in immuno-onology, things are likely to get more confusing rather than less so and it could well be another 3-5 years before things truly settle down and more concrete trends emerge.

Here, we reviewed 10 different areas of interest with a strong clinical relevance and explored the topics further.

Please note that some of these will also have follow-on posts with thought leader interviews and related poster reviews.

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