After several years in the wastelands of cancer research due to lack of significant results and only one product on the market, therapeutic cancer vaccines now look to be back in fashion and are seeing a revival with their inclusion in clinical trials.
One of the reasons behind the resurgence of interest is the advent of checkpoints, and the potential of vaccines in the immuno-oncology space to boost or enhance the immune response.
Their use could not only increase the response to checkpoint inhibitors in people who might otherwise not respond, but in those who obtain some initial response such as a partial response, they could also potentially help achieve a more durable long-term response.
As we continue to ride the wave of cancer immunotherapy on BSB, the cancer vaccine field is suddenly an exciting area to watch.
I’ve long been known as a cancer vaccine sceptic, although recently several approaches in this niche have begun to look rather promising indeed. Here, we highlight and discuss one such company in the field, including an interview with the CEO.
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At the recent Triple (EORTC-NCI-AACR) and ASH meetings, Blueprint Medicines (Cambridge, MA) presented data on some of their targeted compounds in early clinical development including data in KIT, PDGFα and FGFR4 driven cancers.
While many observers attention is currently distracted on cancer immunotherapies, let’s not take our eye off the ball and forget that when we do find driver oncogenes in rare tumours, the activity of TKIs can still be superior in these situations and offer exquisite sensitivity, leading to exceptional responses.
Here, we take stock with a look what Blueprint are doing, where they’re going and also offer some perspectives from senior company executives, whom we interviewed last month.
Which reminds me, someone recently asked why we do so many interviews, “You do a prodigious amount of interviews on BSB, why is that?”
The answer is very simple – to learn faster and share that knowledge with other like minded souls. Charlie Ambler, author of Daily Zen, sums it up well in an essay about Talk Less:
“In Zen tradition, I’d like the kill the Buddha that is Lao Tzu and revise his ancient saying. It’s not that those who talk don’t know and those who know don’t talk— it’s that talking often inhibits us from knowing.”
Thus, the corollary here is that if you undertake interviews with scientists and researchers regularly then you have the pleasure of talking less – the person in the hotseat naturally talks more – and you learn faster.
What’s not to like? We all learn different things depending on our perspective and knowledge base. Sometimes, I even find re-reading old interviews a year or so later while preparing for a new one a related topic teaches me something new I didn’t see or realise before, simply because my own understanding has improved. Hopefully that is also true for subscribers!
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HI Koko Crater Flowers
Over the last week or so, we’ve received a lot of questions on the following topics relating to women’s cancers in breast and ovarian carcinomas:
- APHINITY impact – pertuzumab and neratinib
- PARPs in ovarian cancer – niraparib, rucaparib and olaparib
- Seattle Genetics and Immunomedics
So this is probably a good time for a February BSB Reader Q&A post on the hot topics of the moment in cancer research.
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The huge pile of interesting scientific papers yet to be read seems to breed overnight and one constantly feels like they’re 2,000 articles behind, even with spending Friday mornings attacking them with gusto.
This was as true in my PhD days as it is now. For a scientist, these represent a lifeline and an important necessity, rather than a luxury.
In the last journal club posting we covered some hot topics in cancer immunotherapy, so this one covers a very different topic, namely targeted therapies.
It’s a good time for a new journal club post, where we tackle some of the recent published literature in oncology and highlight some important new findings that could have an impact on cancer research and development.
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At the recent 2016 San Antonio Breast Cancer Symposium (SABCS16), Cascadian Therapeutics (NASDAQ: CASC) presented a poster (Abstract #P4–21–01) on:
“Efficacy Results of a Phase 1b Study of Tucatinib (ONT–380), an Oral HER2-Specific Inhibitor, in Combination With Capecitabine and Trastuzumab in HER2+ Metastatic Breast Cancer, Including Patients with Brain Metastases.”
Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2.
Cascadian’s tucatinib poster at #SABCS16
We’ve seen several new treatments approved for HER2 positive breast cancers in recent years including four targeted treatments: trastuzumab, pertuzumab, lapatinib and T-DM1.
Other companies such as Puma Biotech (NASDAQ: PBYI) also have oral TKIs in development. Puma’s drug, neratinib has, however been shown to have a high incidence of grade 3+ diarrhea, raising questions about its tolerance.
At SABCS16 (Abstract P02–11–03), the company presented the interim analysis of an open-label, multicenter phase 2 trial, which explored their compound:
“Incidence and severity of diarrhea with neratinib + intensive loperamide prophylaxis in patients (pts) with HER2+ early-stage breast cancer (EBC).”
There has been a lot of interest and controversy in this space, so it’s time to take a look at the latest events in HER2+ breast cancer and consider the ramifications since there are a number of new developments that are well worth following, including neratinib (Puma Biotech) and pertuzumab (Genentech).
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San Francisco: In the final post of the week, it’s time to focus on some of the interesting concepts and early ideas being explored in GI tumours such as pancreatic and colorectal carcinomas.
Gems from the Poster Hall or what Dog Drug Heaven really looks like?
Despite the image implied by the used poster bins (right), there were actually several encouraging signs from emerging IO approaches as well as some surprising results that lead to some compounds – or at least some indications – going off to dog drug heaven.
There were also some salutory lessons to be learned in terms of understanding biomarkers and useful these can be.
After years of incremental improvements with targeted therapies, it’s time to look at whether some immunotherapy combinations can make an impact in what is known as cold tumours.
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San Francisco: ASCO Gastrointestinal symposium 2017 – Update on metastatic colorectal cancer
It might surprise quite a few people that colorectal cancer (CRC) is the third most commonly diagnosed cancer globally, especially in the western hemisphere where hereditary, dietary and lifestyle factors can be important.
The bedrock of therapeutic approaches in this disease have largely centred around chemotherapy (FOLFOX or FOLFIRI) along with targeted therapies against EGFR (cetuximab, panitumumab) or VEGF (bevacizumab, ziv-aflibercept, regorafenib etc).
In our second report from #GI17, we take a look at some of the emerging monotherapy and combination approaches that are showing early signs of moving the needle in advanced CRC, an area that has been relatively dormant of late. This is partly because it’s a cold tumour and with the focus on cancer immunotherapies, it’s not the first tumour type that companies will necessarily rush to evaluate.
Things are changing though, even in colorectal cancer so it’s time to look at some key studies that may teach us more about this disease.
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San Francisco: A look at what’s new in gastric cancer (GC) from the 2017 ASCO GI meeting.
Day 1 of #GI17 is filling up…
There were several phase 3 trials presented in GC and gastro-esophageal junction (GEJ) carcinoma in both targeted therapies and immunotherapies this past weekend.
- When we look carefully at the latest data, what do we find?
- Where are the opportunities and challenges in this niche?
Another critical question that many observers will be interested in is…
Will BMS’s checkpoint inhibitor, nivolumab (Opdivo), overcome recent setbacks in lung cancer and make a mark in stomach cancer to challenge approved targeted therapies such as ramucirumab (Cyramza)?
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The most common cause of breast cancer death is when metastatic ER+ tumors develop resistance to treatment. There remains an huge unmet medical need for new effective treatment options.
One translational clinical researcher leading the way in understanding the molecular and genomic landscape in ER+ metastatic breast cancer is Nikhil Wagle, MD (@Nikhilwagle), Deputy Director, Center for Cancer Precision Medicine at the Dana-Farber Cancer Institute (DFCI).
He’s shown the power of partnering with patients via social media to speed research, with over 3,000 men and women joining the Metastatic Breast Cancer Project that launched in October 2015.
At the 2016 San Antonio Breast Cancer Symposium, Dr Wagle kindly spoke to BSB about the genomics research that he and colleagues are undertaking, and what this may mean for how metastatic breast cancer is treated:
- What if you could help accelerate clinical trial enrollment via a network of educated and empowered patients?
- What if you could access real world data to help learn about exceptional responders?
For those of you in Pharmaland, here’s one approach that should captivate the imagination of what’s possible.
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Dr Max Wicha is the 2016 recipient of the AACR Distinguished Lectureship in Breast Cancer Research. At the 2016 San Antonio Breast Cancer Symposium (SABCS16) he gave his award lecture, “Targeting Breast Cancer Stem Cells: Challenges and Opportunities.”
SABC16 Dr Max Wicha Award Lecture
As the AACR press release notes, “This lectureship recognizes an outstanding scientist whose work has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment or prevention of breast cancer.”
Dr Wicha is a pioneer in the field of cancer stem cells, and is Director Emeritus of the University of Michigan Comprenhensive Cancer Center and a co-founder of OncoMed Pharmaceuticals (NASDAQ: OMED).
Targeting cancer stem cells is an area I expect we will hear a lot more about, particularly in breast cancer. Dr Wicha kindly spoke to BSB after his award lecture, which was one of my highlights of SABCS16.
In case you missed it, do check out the post from the 2016 EORTC-NCI-AACR Molecular Targets Symposium in Munich that featured Dr Mina Bisell (Berkeley), who was a previous recipient of the AACR Distinguished Lectureship in Breast Cancer Research award in 2012 (Link.)
This is the fifth in our series of expert interviews from the 2016 San Antonio Breast Cancer Symposium.
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