As the weather heats up in the western hemisphere, the temperatures are not the only thing increasing…
In Pharmaland, the oncology space traditionally sees either interesting new data published or a spate of post American Society of Clinical Oncology (ASCO) filings. The summer doldrums often give way to a faster pace in the fall.
One thing we have been following over the last two years is the T790M race to market in EGFR mutant lung cancer. Clovis Oncology announced last week that they have begun their rolling NDA submission for rociletinib (CO–1686), but what about their keen rival, AstraZeneca with AZD9291?
The company presented new data for AZD9291 jn the EGFR mutant lung cancer upfront setting, but no formal announcement was made about the regulatory status.
There are some potentially interesting new developments to report here, though.
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Yesterday, Juno Therapeutics and Celgene announced a ten year collaboration that is expected to close in July-August. In short, Celgene has exclusive right to entire the Juno portfolio in oncology and auto-immune cell therapy products in development outside North America and co-promote certain programs globally (not specified). Juno, meanwhile, gains the option to co-develop and co-promote select Celgene programs (also not specified).
You can see the terms of the deal here.
And listen to the webcast from the call after hours.
This news comes hot on the foot of an earlier announcement that the FDA accepted the Juno IND for JCAR017, a CD19 CAR T cell therapy being developed in relapsed/refractory NHL scheduled to initiate in 2015, with the possibility of a registration trial commencing in 2016.
What was fascinating, however, was the BioTwitter reactions last night – predictably, people either loved or hated the news – it clearly came as a surprise to many.
This morning my inbox is full of questions on this dramatic topic from subscribers, so here are some topline thoughts on this issue to answer the questions coming in.
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Many years ago, I used to work in the sarcoma and GIST space, which is a very interesting and fascinating disease to explore from a biology perspective. There are many different subsets of sarcoma, several different histologies, as well as numerous targets such as KIT in gastrointestinal stromal tumours (GIST). Some of these subsets are sensitive to chemotherapy such as doxorubicin, while others such as GIST are sensitive to targeted therapies including imatinib, sunitinib, regorafenib etc. Imatinib (Gleevec) is particularly effective in GISTs with exon 11, while the less common exon 9 has been shown to be more sensitive to sunitinib (Sutent), for example.
Often pharma companies will work with the Sarcoma Alliance for Research through Collaboration (SARC) cooperative group to undertake a phase 1 allcomers trial to evaluate which subsets might be appropriate for a given therapy, before exploring a narrower inclusion/exclusion criteria in a larger phase 2 or 3 study. You can check out their current clinical trials in sarcomas here.
Overall, people with malignant sarcomas tend to be seen by specialist centres where there are usually clinical trials available, representing a way to determine which of the agents in development are superior to the current standard of care.
Dr Margaret von Mehren
One of my favourite moments at ASCO this year was escaping the heavily mobbed poster halls to sit down for a quiet ‘fireside chat’ and catching up with an expert in this field to learn more about the latest new developments in sarcoma.
I’m delighted to publish another thought leader discussion today on Biotech Strategy Blog (BSB), where we have an in-depth interview with Dr Margaret von Mehren, the Director of Sarcoma Oncology at Fox Chase Cancer Center. She has spent spent her career trying to identify new therapeutics for gastrointestinal stromal tumours (GIST), as well as soft tissue sarcomas (STS).
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In today’s post, it’s time to address a bunch of questions we’ve received over the last few weeks from subscribers about the latest and – not so greatest – in cancer research.
ASCO 2015 Chicago
Sometimes these queries are fairly straightforward to answer, other times requires some sleuthing and hunting down thought leaders for some additional context and insights… For obvious reasons, these folks are best caught in person at cancer conferences such as AACR and ASCO. The feedback isn’t always sparkly and positive though, it can also be gloom and doom, just like the inclement weather!
So here goes, questions on the following are covered in the article below:
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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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We’ve heard a lot about agents that target the PD–1/PD-L1 pathway over the last two years, in particular, from:
- Nivolumab (BMS)
- Pembrolizumab (Merck)
- Atezolizumab (Roche/Genentech)
- MEDI–4736 (AstraZeneca/MedImmune)
What about other agents against this pathway that are in earlier development? It really doesn’t take long for a new space to become quickly crowded and very competitive, as the Pharma R&D machines start cranking out results from clinical trials.
A critical question that will to be considered is how will the third, fourth or even 19th agent to market differentiate themselves from those already approved and established? Is it realistic to expect a blue ocean strategy approach or will the pieces of the pie become ever smaller?
At the annual meeting of the American Society of Clinical Oncology (ASCO) earlier this month, there was new data presented from other companies on checkpoint inhibition. We took at look at some of the emerging data in more detail.
To learn more about the increasingly competitive anti-PD1/PDL1 pathway market, check out our insights in the mini report below.
One interesting aspect of the recent American Society of Clinical Oncology (ASCO) meeting was the surprise many people expressed in conversations that chemotherapy might actually be useful in combination with checkpoint inhibitors.
You see, several years ago when we first started writing about this new class of agents, I remember vividly how quite a few analysts grumbled on social media or sent me snarky personal messages when it was even suggested that this — along with combinations with existing targeted therapies — might be a worthwhile and valid approach to explore. Clearly they believed that immunotherapies (as monotherapy) were going to be the ultimate panacea.
Not so fast…
There are a number of scientific reasons for combination strategies, but not everyone thinks rationally when new approches come along and their attititude is often ‘out with the old, in with the new!’ It was actually quite amusing to see some of the very same folks in Chicago now eulogising the combination of checkpoint blockade with… chemotherapy in lung, colorectal or even bladder cancer.
One reason why these traditional therapies may be important is because they can influence the tumour microenvironment in both positive and negative ways. That can be helpful for deciding on rational future combinations, rather than just throwing mud at the wall and hoping based on a limited set of data.
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Chicago – the 2015 annual meeting of the American Society of Clinical Oncology (ASCO) is underway. It’s the Super Bowl of clinical cancer research with approx 35,000 attendees from all over the world.
Earlier today, in a press briefing focused on cancer immunotherapy, we had a glimpse of some of the data that ASCO thinks is particularly newsworthy at the meeting.
In this post, we’ll offer some top-line thoughts and commentary on the following presentations by:
Dung T. Le “PD-1 Blockade in Tumors with Mismatch Repair Deficiency”
Anthony B. El-Khoueiry “Phase 1/2 Safety and Antitumor Activity of Nivolumab in Patients with Advanced Hepatocellular Carcinoma (HCC): CA209-040
Tanguy Y. Seiwert “Antitumor Activity of the Anti-PD-1 Antibody Pembrolizumab in Biomarker-Unselected Patients with R/M Head and Neck Cancer: preliminary results from the KEYNOTE-012 Expansion cohort.”
Luiz Paz-Ares “Phase III, Randomized Trial Checkmate 057 of Nivolumab (NIVO) versus Docetaxel (DOC) in advanced Non-Squamous (non-SQ) cell Non-small Cell Lung Cancer (NSCLC).
We’ll be writing a daily post from ASCO 2015 with regular updates on sessions we’ve attended, and initial thoughts and reactions. Our usual in-depth coverage will follow after the meeting.
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Yesterday, Juno Therapeutics announced a new deal for a collaboration with Editas Medicine that is:
“Focused on creating chimeric antigen receptor (CAR T) and high-affinity T cell receptor (TCR) therapies to treat cancer. The companies will pursue three research programs together utilizing Editas’ genome editing technologies, including CRISPR/Cas9, with Juno’s CAR and TCR technologies.”
This follows on from their recent deals with Fate Therapeutics and Stage Cell Therapeutics and bluebird bio’s licensing deal with Five Prime for novel antibodies to develop CAR T cell therapy.
One of the most interesting questions in CAR T cell development, is whether you need to incorporate a suicide gene or suicide switch into them that allows you to turn off the response, force the T cells to self-destruct, in the event of severe Cytokine Release Syndrome (CRS) or other serious adverse events.
This review article is another example that straddles data from conferences earlier this month at Immunology 2015 (AAI) and American Society of Gene and Cell Therapy (ASGCT) with the American Society of Clinical Oncology (ASCO) this coming weekend.
At ASGCT we spoke with Dr Carl June and also heard the latest update on what Cellectis are doing from Dr Julianne Smith.
Companies mentioned: Juno Therapeutics, Novartis/U Penn, Cellectis, Bellicum, bluebird bio, Formula, Molmed.
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Have you ever sat in a freezing cold scientific session and been so engrossed in the compelling presentations that followed, you simply forgot to take notes? Not one. That actually happened to me at the American Association for Cancer Research (AACR) in Philadelphia this year in one of the many fringe sessions that I attended.
Reading Terminal Clock, Philadelphia
Granted, the hot topic of the conference was undoubtedly checkpoint inhibition, but I was anxious to escape to the comfort of some meaty and familiar basic and translational science, namely MYC. MYC is largely thought to be a difficult to target, even undruggable protein, and along with RAS and p53, represents a formidable challenge for cancer researchers. These three oncogenic proteins alone are probably responsible for more drug resistance developing and even death from cancer than any other proteins in a patient with advanced disease.
For cancer patients with advanced disease, the clock is ticking on time they have left.
Solve these three problems (MYC, RAS and p53) and we may have a shot at dramatically improving outcomes. As Dr Gerard Evans (Cambridge) noted:
“I think it’s fair to say that we don’t really know why interruption of any oncogenic signal actually kills cancer cells, but one of the reasons that we’re interested in MYC is because it seems to be a common downstream effector of many, maybe all cancers.”
Sure, the road to success is paved with an enormous graveyard of failures, just as metastatic melanoma was before checkpoint blockade came along, ironically. What I heard at AACR both inspired and filled me with greater confidence… we’re finally getting somewhere.
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