For what seems the longest time, we have seen the battle in metastatic clear cell renal cell carcinoma (ccRCC) being focused on various anti-VEGF TKIs, whether against interferon, mTOR inhibitors, and even each other.
Lately, anti-PD(L)1 antibodies have also come on the scene – both as monotherapy and in different combinations – so are things set to change?
Will it be plaining sailing or are there hidden dangers ahead for the unwary?
Here, we take a look at the ever evolving landscape in RCC and explore the issues and challenges surrounding some of the novel combination readouts, including a look at the role immuno-oncology might play going forward.
Not surprisingly, there’s a lot to consider, discuss and think about…
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San Francisco – Yesterday at the ASCO Genitourinary Symposium, Dr Kim Chi noted that emerging data suggests that ctDNA appears to give better picture of tumour mutations than biopsy and can also monitor tumour load. This is an encouraging development that may facilitate increased use of the diagnostic as a helpful biomarker of response in clinical trials with immune checkpoint blockade.
We also know that prostate cancer sits firmly in the middle of the now famous Alexandrov and colleagues tumour mutation burden (TMB) analysis, but what factors are important in our understanding of the underlying biology of the disease?
There are many inhibitory factors exerted on the tumour microenvironment and thase may vary not only by tumour type e.g. renal cell carcinoma may have a greater influence from VEGF than prostate cancer, but also in individual patients.
With this in mind, I wanted to explore some new combination data being presented at the meeting, as well as look aspirationally to some potential combinations currently in development that may have escaped many people’s attention.
In this post, we take a look at current and future implications that keen observers should be watching out for…
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Red Bull Air Race NYC
San Francisco: Today at the 2018 American Society for Clinical Oncology Genitourinary Cancer Symposium, commonly known as ASCO GU (Twitter #GU18), Dr Eric Small (UCSF) will present the results of the SPARTAN phase 3 trial (Link to abstract):
SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Despite the fact this is a positive trial and apalutumide will most likely gain regulatory approval for this indication in the United States, the data presented at ASCO GU is not a winner when viewed in the broader context of the prostate cancer landscape.
BSB subscribers can login to understand why, and also gain the perspective of a global thought leader familiar with both the SPARTAN and PROSPER trial data.
On a day when J&J have just announced that abiraterone (in combination with prednisone) provides a new treatment option for patients with metastatic high-risk castration-sensitive prostate cancer based on the results from the randomised phase 3 LATITUDE study, everyone’s attention is focused on the battle between SPARTAN (apalutamide) and PROSPER (enzalutamide) in M0 disease.
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For the last couple of years at every annual meeting of the American Society of Hematology (ASH) conference, I have posted an extensive Preview of the CAR T cell therapy landscape and looked at which abstracts piqued my interest.
The roaring 30s CAR
This year the review is the most extensive to date, with more companies, more research groups, more tumour types and way more preclinical research coming through. It’s like a kaleidoscope of ideas cascading through R&D.
The other thing to take note is how fast the field is moving – it’s warp speed now and so much comes through the literature every month on top of that.
So here we go – hold onto your hats as there is a LOT to contemplate this year!
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As we move from monotherapies to combinations in the immuno-oncology space, we start to see some intriguing ideas being explored from additional checkpoints to vaccines to neoantigens to immune agonists to oncolytic viruses. There are numerous ways to evaluate how to boost or jumpstart more immune cells upfront in the hope of seeing better efficacy.
One way to do this is to better understand the tumour microenvironment.
Wall of people at ASH16 in San Diego
If we know what’s wrong under the hood, we might be better able to make the immune system get going… more gas, faulty starter motor, dead battery, loose wire, broken fan belt? All these things and more might be a problem so you can see that diagnosing the issue up from from basic and translational work might be instructive for clinical trials.
If you don’t know what problem you’re trying to fix or repair then you might as well be throwing mud at the wall. Just as we don’t expect a car mechanic to suggest changing the battery or starter-motor without first diagnosing the issue, so understanding the tumour microenvironment in each different cancer or disease might also be a helpful strategy.
At the recent American Society of Hematology annual meeting (#ASH16), there was a fascinating sceintifc workshop that focused on this very concept – what’s going on under the hood and how do we go about fixing it?
Here we explore these ideas via an interview with a thought leader and specialist in the field. What he had to say was very interesting and candid indeed.
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Some cancer conferences attract more questions and queries than others.
Old Town San Diego
Interestingly, ASH is always a popular meeting for attendees and readers alike, so it is good to see another batch of critical questions come in so soon after the last one. It’s a while since we did two BSB reader Q&A mailbags from a single meeting!
Not surprisingly, there were also a bunch of questions on CAR T cell therapies, which continue to dominate readers minds, as well as related issues. Here, we answer the most pressing questions that have come in over the last week.
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San Diego – after “Flying Friday” where I flew from Munich to San Diego, Biotech Strategy Blog coverage of the 2016 annual meeting of the American Society of Hematology (ASH) is now done for another year.
With over 27,000 attendees – it’s the largest ASH annual meeting I’ve seen in 20 years of coming here! ASH is definitely the pre-eminent global meeting for hematology and blood cancers.
As you might expect, the thought leaders at this event are super-busy, but we’ve already managed to catch up with a few, and we’ll be rolling out interviews in the “post-game show.”
Subscribers have been asking what’s really hot at ASH this weekend, so reflecting my interests and the sessions I went to, here are my seven highlights/learnings of ASH 2016 (so far). There’s a lot more data to come!
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It was only five years ago that the number of abstracts on CAR T cell therapies at the American Society of Hematology (ASH) ran to a dozen or less. Fast forward to 2016 and we now have tens of them, almost too many to count, let along review quickly and easily.
A scene from ASH 2015…
To give you an idea of the staggering speed of progress, in 2010 it took me less than half an hour to search and read all the CAR T cell abstracts, now it takes nearly a whole day to peruse and review them carefully.
We can’t resist a challenge…
As usual, we will write in more depth from the meeting as the data emerges in real time since many of the abstracts are often placeholders with updated information provided at the conference itself.
For now, here we provide an in-depth preview of the CAR T cell landscape in terms of the players, the products, new scientific research, biomarkers, emerging trends and more in a handy What to Watch For (W2W4) guide on key areas to expect at ASH to enable better enjoyment and awareness as the data rolls out next month.
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There was a time when it seemed that all the good news emerging in cancer research was on breast cancer, that is clearly no longer true as other tumour types have seen some leaps and bounds with different modalities, including areas previously thought to be a graveyard for big Pharma, such as metastatic melanoma, for example.
New Dawn at the Houses of Parliament
That said, after the excellent developments in hormone-sensitive disease and the identification of the HER2 oncogene, we now have CDK4/6 as a validated target in metastatic breast cancer.
Pfizer’s palbociclib (Ibrance) lead the way, with two approvals in previously untreated and relapsed ER+ HER2- advanced breast cancer. Two other companies in this field are Novartis with ribociclib and Lilly with abemaciclib. Data is being presented on all three therapies at ESMO this year.
In addition, there are some other abstracts of note that are well worth discussing.
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In our ECCO Preview series last year (note: ESMO and ECCO have alternated the EU major cancer conference in the Fall for years), we highlighted several promising novel agents in development including the following:
- StemCentRx’s anti-DLL3 inhibitor: rovalpituzumab tesirine (ROVA-T)
- Ignyta’s Pan Trk, ROS1 and ALK inhibitor: entrectinib
- Pfizer’s anti-NOTCH3 inhibitor: PF–06650808
- Pfizer’s PTK7 ADC in TNBC: PF–06647020
What happened to them all? Were they good selections or not?
Well, AbbVie acquired StemCentRx in a $10.2B deal, Ignyta are busy advertising their new clinical trial enrollment for entrectinib as a non-chemotherapy and non-placebo controlled study on social media, suggesting that compound’s clinical development is still very much alive, while both the Pfizer compounds are also still active, as far as I know.
None have yet been consigned to dog drug heaven, which is quite something considering the failure rate in oncology drug pipelines!
Indeed, last year the Pfizer PTK7 ADC data was focused on triple negative breast cancer, where there is a solid rationale. This time around, the same research group explore the latest activity in advanced solid tumours, including ovarian cancer, as mentioned in the earlier Preview (See: 9 key abstracts in Ovarian Cancer).
So it’s time to sit down and chew the fat on one of my favourite topics at conferences – Development Therapeutics.
Here we consider which other compounds – other than the Pfizer ADC – that are worthy of highlighting and watching out for this year?
There are certainly some curious and quite different (i.e. novel) approaches to look at.
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