In a landmark publication today, the prestigious journal Nature includes five “Letters” regarding checkpoint blockade of the programmed death-1 (PD-1) receptor and its ligand PD-L1. It confirms the promise and potential of the emerging field of immuno-oncology to provide durable and long lasting responses in many cancers.
Readers of the blog will already have read about the stunning early data presented at ASCO this year for the engineered humanized antibody MPDL3280A (Genentech/Roche) in urothelial bladder cancer (UBC). In his Nature Letter, Thomas Powles (Barts) and colleagues sum of the significance of this data in the opening sentence:
“There have been no major advances for the treatment of metastatic urothelial bladder cancer (UBC) in the last 30 years.”
On the basis of this data, MPDL3280A received Breaththrough Therapy Designation from the FDA earlier this year.
Roy Herbst (Yale) and colleagues in their Nature Letter write about biomakers of PD-L1 inhibition and how their data “suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is reinvigorated on antibody treatment.”
At the recent annual meeting of the Society for Immunotherapy of Cancer (SITC), Dr Herbst gave one of the best presentations of the meeting, in which he discussed “Personalized Immunotherapy for Non-Small Cell Lung Cancer.” His top ten lessons learned kept the audience’s attention throughout.
In this excerpt from an interview he kindly gave BSB afterwards, he talks about the promise of cancer immunotherapy in lung cancer:
Tomorrow is the Thanksgiving holiday in the United States, so this will be the only post this week. Thanksgiving is a good time to take a moment out of the hectic life we all live to “smell the roses” and express gratitude for all the positive things around us.
Next week sees the start of the American Society of Hematology (ASH) annual meeting in San Francisco. The cancer conference circuit seems to roll quickly from one meeting to the next at the moment. There’s a lot of promising data, and while we can’t discuss the data before the meeting due to ASH embargo restrictions, next week we will be highlighting some of the presentations we are particularly looking forward to.
Subscribers can login below or you can purchase access to read more detail about all five Nature Letters, and their implications for the emerging field of immuno-oncology.
The Society for Immunotherapy of Cancer (SITC) annual meeting promises to be a most interesting one, if the first day is anything to go by. It’s being held this week at National Harbor, Maryland on the banks of the Potomac River just south of Washington DC.
As the meeting started with some intensive workshops yesterday, the American Society for Hematology (ASH) annual meeting abstracts were released at 9am, giving up a choice between writing up SITC in situ or switching gears and analysing the initial hematology abstracts. In the interests of sanity, we have decided to focus on SITC for the next week, then move onto the AACR-NCI-EORTC conference, before reviewing the ASH data in detailed previews.
SITC is mostly a translational science meeting with a little bit of relevant clinical data through in here and there. It’s also not for the faint hearted, especially given the sheer intensity and pace of some of the talks – keeping up with pen and paper to hastily scribble notes is surprisingly quite hard!
It was an honour to attend as one of the few members of the media here. The excitement is palpable, with speakers reminding us of how only a few years ago, few people attended immunotherapy sessions at ASCO. SITC is rapidly becoming a major meeting with a record-breaking 1500 expected for the first time! It is the immuno-oncology meeting to attend for those interested in understanding the emerging trends, landscape and direction that research is taking us.
Yesterday SITC fielded two workshops with impressive line-ups from the immuno-oncology space that included Drs Carl June, James Allison, Tom Gajewski, Susan Topalian, Stephen Hodi and Mario Sznol, to name a few. The workshops focused on different topics:
- A basic one on understanding the immune system
- A more advanced one on combination strategies in immunotherapy
Rather than summarise all the talks from both sessions that ran a full day each, we’ve decided to focus on some themes, ideas and concepts that catch our attention each day. Here’s the first of our daily reviews from the SITC 2014 annual meeting. Thanks to all our subscribers whose support enabled us to attend this meeting for the first time.
To learn more about our impressions from the SITC immunotherapy workshops yesterday, you can sign in or sign up below.
Cancer immunotherapy, the ability to harness the body’s own immune system to fight cancer, is showing early promise in bladder cancer.
“Breathing new life into bladder cancer treatment” was the title of the excellent discussion by Maria De Dantis (Vienna) of data presented at the recent ESMO Congress in Madrid.
Advanced bladder cancer has a particularly poor prognosis. Once the cancer has spread in the body, according to Cancer Research UK, the average survival time is approximately a year to 18 months.
There is clearly an unmet medical need for effective new treatments, with no major treatment advances for over 30 years. To date, targeted agents in the second-line setting have shown only incremental progression free survival and generally low overall response rates.
Which is why it’s exciting to see hope for patients with urothelial bladder cancer from new inhibitors of the PD-1 immune checkpoint signalling pathway.
At ASCO this year, data for Roche/Genentech’s anti PD-L1 (MPDL3280A) was presented (Abstract 5011) by Thomas Powles (Barts, London). Commenting on the data, in her post “Making a difference in advanced bladder cancer” Sally noted, “it wouldn’t have been out of place in the Plenary session, frankly.”
Recognizing the potential based on the promise of the early clinical data, on May 31st the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to MPDL3280A in bladder cancer.
If you need to catch up on immuno-oncology, we have a growing library of posts on Biotech Strategy Blog, and we’ll be continuing our coverage of the rapid progress in this area at the forthcoming annual meeting of the Society for Immunotherapy of Cancer (SITC), which takes place at National Harbor, MD from Nov 6 -9.
At ESMO 2014, phase 1 clinical trial data in bladder cancer was presented for both Pembrolizumab (Merck) and MPDL3280A (Roche/Genentech).
Subscribers can login in to read how the two drugs compared in this indication, or you can purchase access by clicking on the blue icon below.
Over the last few days, we’ve covered data from the leading checkpoint inhibitors from BMS, Merck and Roche, but what about other agents in development in immuno-oncology? One of the companies that burst on the scene in Chicago at ASCO 2014 with solid data was AstraZeneca with their anti-PD-L1, MEDI4736.
To put progress in context, last year Merck had one single abstract for MK–3475 (pembrolizumab), whereas this year MEDI4736 debuted with 7 abstracts, including several Trials in Progress posters in combination with their anti-CTLA4, tremelimumab, plus some important oral presentations too.
The last morning of the final day of the ASCO conference has not exactly been well attended in past years, especially in Developmental Therapeutics. This year was different – the large hall was jam packed and it was standing room only. I was lucky to get one of the last seats in the front row a good 15–20 mins early!
As we were waiting for the proceedings to start, the Japanese doctor sitting next to me turned and said:
“What do you think of this compound? I’m not expecting much, and they are behind the others already!”
To learn more about my insights from ASCO 2014, you can sign up or sign in below:
The melanoma oral abstracts session at ASCO 2014 was packed as a full house in the Arie Crown lecture theatre listened to the latest on new immuno-oncology therapies that are leading a revolution in melanoma treatment.
In the Clinical Science Symposium on PD-1 blockade and in the oral session at ASCO 2013 we heard how PD-1 antibodies nivolumab, MK-3475 (now pembrolizumab) and the PD-L1 antibody MPDL3280A had high response rates, long durations of response with favourable toxicity. This led to melanoma suddenly becoming one of the hottest areas of cancer drug development.
Global incidence of stage III melanoma continues to rise, with a high 5 year relapse rate (89% in stage IIIc), so there remains a need for more effective treatment options. It’s particularly sad to see so many young people end up with metastatic melanoma from over-exposure to tanning beds or too much sun! After going to several melanoma sessions, I don’t go out as much in the mid-day sun here in Florida.
So what did latest data show at ASCO 2014? Is pembrolizumab better than nivolumab? Will combinations be more effective than single agent therapies alone and will toxicities impact the risk:benefit profile?
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Chicago – it’s the last day of the American Society of Clinical Oncology (ASCO) annual meeting. There’s been a record attendance this year with over 30,000 people coming to Chicago to hear the latest news and research on cancer treatments.
The message I am left with is the considerable hope it offers cancer patients around the well as researchers harness the latest techniques in genome sequencing and through a deeper understanding of cancer biology, develop new targets and ways of attacking this disease. Attacking the immune system (immuno-oncology) is one of the most exciting areas in cancer drug development.
I only wish other areas of biomedical research where there is an unmet need e.g. new and effective treatments for neuro-degenerative diseases such as Alzheimer’s, offered such hope and focused research activity.
It’s the final day of ASCO 2014 and only the diehards are left (or those who couldn’t get a plane out early). We hope you’ve enjoyed the “live” blog and our notes from the road each day.
What are we covering this morning? Subscribers can login below or sign up to find out more.
Cancer immunotherapy was described in the December 20, 2013 issue of Science magazine as their Breakthrough of the Year, but really, we are just scratching the surface of what can be achieved.
“We are at beginning of a REVOLUTION in immunotherapy,” said Elizabeth M. Jaffee, MD at the start of American Society of Clinical Oncology GastroIntestinal (ASCO GI) symposium keynote lecture on Immunologic Treatments for GI Cancers.
Elizabeth M Jaffee, MD
Jaffee likened the revolution in immunotherapy to the same excitement the Beatles brought to music, or the same magnitude of technology advances made by Apple.
Dr Jaffee is the Dana and Albert “Cubby” Broccoli Professor of Oncology at Johns Hopkins, and has developed a number of vaccines including GVAX, which is currently licensed to Aduro Biotech.
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