One of the frequently cited conceptual frameworks in Cancer Immunotherapy is the Cancer Immunity Cycle developed by Drs Dan Chen and Ira Mellman from Genentech.
Ira Mellman and Dan Chen
As we heard Dan and Ira tell us on the Novel Targets Podcast recorded last year at #AACR16, the cancer immunity cycle doesn’t include all the elements that we now know impact the immune system and whether someone will have an immune response. The microbiome is one example that readily comes to mind.
To address this, Chen and Mellman have now published the next installment in the series in Nature:
“Elements of Cancer Immunity and the cancer-immune setpoint.”
The review paper published last month incorporates the latest research into a different framework that looks at the factors that influence what they call the ‘cancer-immune setpoint.’
Anyone involved with cancer immunotherapy knows how fast moving and dynamic the field is, something they draw attention to:
“The pace of cancer immunotherapy clinical studies is such that they have outstripped our progress in understanding the underlying science. However, this situation has created the opportunity to combine emerging scientific and clinical insights in a synergistic fashion that… will also provide guidance for the identification of new targets… and the crafting of a framework for making decisions on a personalized basis.”
Conceptual frameworks such as those proposed by Chen and Mellman will be of increasing importance as we try to make sense of the tsunami of cancer immunotherapy clinical trial data, including combinations, that is coming our way over the next 18 months.
During my recent visit to San Francisco for ASCO GI, I had the great pleasure to catch up with Daniel S. Chen, MD PhD, (Global Head of Cancer Immunotherapy Development, Genentech/Roche) and talk about his latest thoughts on how we should think about cancer immunotherapy.
In writing these review papers he told me:
“We look at this as an opportunity to really think about the field, and try to conceptualize what is happening.”
We also discussed their collaboration with Kite Pharma, something of relevance to conferences this week as we head off to BMT Tandem and the ASCO-SITC meeting.
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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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It’s Day 7 of our 12 day Countdown to AACR 2016 in New Orleans. After exploring GITR and OX40, we’re now looking at another stimulatory target for cancer immunotherapy: CD40.
We’ve been writing about CD40 as a cancer immunotherapy target for some time. See posts: “CD40 as a Cancer Immunotherapy Target” and “Targeting CD40 in Cancer Immunotherapy.”
Anti-CD40 antibodies are agonists that act on stimulatory signalling receptors on T cells and antigen presenting cells (APCs). Targeting CD40 effectively acts to “put the foot on the gas” and may help generate a better immune response. This could be important in cancers that have fewer natural T cells present.
CD40 is an attractive target because it’s expressed in more than 50% of carcinomas and melanomas and almost all hematological B cell malignancies. Of particular interest is the potential to combine a CD40 agonist with a PD-1/PD-L1 checkpoint inhibitor.
Multiple companies have CD40 agonists in clinical development including Roche, Apexigen, Alligator Biosciences and Seattle Genetics. There are others coming too.
In this preview of AACR 2016, we’re looking at the CD40 landscape. New products and companies have entered the scene, so we’re highlighting them and some of the CD40 presentations to look out for at AACR 2016 (and why they matter).
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It’s Tuesday at the 2016 JP Morgan Healthcare conference in San Francisco (Twitter #JPM16).
Each day of #JPM16 we’re doing a rolling blog post which we’re updating throughout the day with commentary and insights on the company presentations we’re covering.
While we’re not giving a blow-by-blow account, many companies have the slides readily available, we will be commenting on noteworthy news, and what we learn about corporate strategy going into 2016.
For those of you who like to catch up with the final summary of each day’s highlights, you can read yesterday’s Day 1 synopsis here and our interview with Seattle Genetics CEO, Clay Siegall here.
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It’s Day 1 of the annual pilgrimage to San Francisco for the JP Morgan Healthcare conference. In light of the success of the daily rolling blogs we’ve done around the conferences we cover, for the first time we’re doing a rolling blog for each day of #JPM16.
Throughout the day (schedule permitting) we’ll be updating the post with commentary around noteworthy news.
Company presentations mentioned in this post include: $PBYI, $CELG, $GILD, $INCY, $SGEN, $MDVN. There’s also commentary on several of the deals announced by Roche, Juno, Novartis, Sanofi, AstraZeneca & Merck.
If you want to follow along yourself, here’s the link to the JPM16 webcasts & conference agenda.
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There are now several CD40 agonist antibodies in early clinical development from several different companies, including:
- Roche – RO7009789
- Apexigen – APX005M
- Seattle Genetics – SEA-CD40
- Alligator Bioscience – ADC–1013
This post is the last in our cancer immunotherapy coverage from the European Cancer Congress in Vienna. It features excerpts from an interview with Dr Christian Rommel, head of oncology discovery at Roche in Basle, Switzerland in which he talks about the development of their CD40 monoclonal antibody. Readers may recall we wrote about this from SITC 2014 last year: “Targeting CD40 in Cancer Immunotherapy.”
This post is also a new primer on CD40 as we start our coverage of the Society for Immunotherapy of Cancer (SITC) 2015 annual meeting. We’re informed by SITC it’s a sell out conference with 600 more people than last year’s record breaking number. Cancer Immunotherapy is indeed the hottest topic in cancer drug development.
If you have plans to be at National Harbor this week, we hope to see you there!
One thing has become very clear in the oncology space over the last year… checkpoint inhibitors are insufficient on their own for the vast majority of tumour types and patients that they have been explored in to date. There are a number of reasons for this, but the main one is lack of T cells in the tumour, which enable an effective immune response to be mounted.
This begs the question – how can we address that issue and manipulate the tumour microenvironment in our favour, thereby making subsequent checkpoint blockade more effective?
There are a number of different ways to do this.
In the past, we’ve discussed several methods including innate immunotherapies such as Aduro’s STING or Biothera’s immunotherapeutic, Imprime PGG. Other approaches include vaccines, which we have discussed in detail, t-cell receptors (TCR) or even monoclonal antibodies, such as AdaptImmune’s approach with their ImmTac technology.
There are other novel strategies currently being investigated by numerous companies too.
In this article – and also the second part of the latest miniseries – which will post tomorrow, we straddle our final reviews of interesting data from the European Cancer Conference (ECC) in Vienna with the upcoming one from the Society of Immunotherapy for Cancer (SITC) being held in National Harbor, Maryland.
Today’s post explores the concept of immunocytokines, engineered antibodies that are designed to boost the immune system, so that subsequent therapies will be more effective.
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At the 2015 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting Barcelona on Friday, Dr Stephen Hauser (UCSF) presented the data for octrelizumab, an anti-CD20 monoclonal antibody, on behalf of the investigators in the OPERA trial. This study compared octrelizumab to a standard of care at the time the study started i.e. IFN β-1a (Rebif).
Roche previously announced that ocrelizumab is the first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis (MS):
- Ocrelizumab showed superiority to interferon beta-1a (Rebif®) in two identical Phase III studies in people with relapsing multiple sclerosis (MS), the most common form of the disease.
- Ocrelizumab is the first investigational medicine to show efficacy in people with primary progressive MS in a large Phase III study.
In addition, Dr Montalban presented the latest data for octrelizumab in primary progressive MS versus placebo (there are no approved therapies for this segment) on behalf of the ORATORIO investigators.
Here on BSB we have extensively covered other anti-CD20 monoclonal antibodies such as rituximab, ofatumumab and obinutuzumab in oncology indications specifically associated with hematologic malignancies, so what’s special about this same target and the results in MS with a different chemical entity?
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Sarcoma is something we call one disease but actually represents 50-70 different histologies, which poses challenges for drug development. Not only do you have to identify what’s the unique target, but it’s hard to accrue patients into trials, when a major center may only see a few of each sub-type.
Soft tissue sarcoma is an area of unmet medical need, and one I have been interested in since launching Gleevec in GIST (way back when) when I was fortunate to get to know many of the leading sarcoma experts.
George D. Demetri, MD. Photo Credit: DFCI
One of these is Dr George Demetri, who is Director, Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.
At the recent European Cancer Congress in Vienna, I had the privilege to talk with Dr Demetri about some of the latest research in soft tissue sarcoma.
We spoke about cancer immunotherapy, new small molecules and monoclonal antibodies, and the potential of targeting the epigenetic machinery.
A lot of what Dr Demetri is doing is currently “under the radar” and while he didn’t give any secrets away, he did give some sense of where some breakthroughs may occur in the not too distant future. He also talked about how sarcomas with a specific target can be used for proof of concept clinical trials of novel agents.
Given the pressure that many companies are under to speed up their path to market strategies, accelerated approval in a rare tumour subset is one approach that can be considered.
It’s an exciting time in the field with the potential for several agents in development to move the needle and make a difference. I hope you enjoy this post, it was a real pleasure to talk with Dr Demetri again.
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It’s time for the August mailbag where we answer questions about cancer research and R&D from subscribers.
After the recent queries about immuno-oncology, it’s time to focus a little on targeted therapies again. Neither chemotherapies nor targeted therapies are going to go away – they are still the bedrock of many treatment approaches in the clinic today. Sadly though, much of the new data for the latter trials were easily swamped by the sheer tsunami of immunotherapy data in Philadelphia (AACR) and Chicago (ASCO).
One important area that we have been discussing on both blogs for some time is the value of well designed basket trials. It’s time to revisit this concept in the light of new data relating to the BRAF V600 mutation outside of metastatic melanoma.
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