Immune checkpoint inhibitors that target CTLA4, PD1 and PDL1 can generate prolonged responses in a minority of patients, but the results so far in prostate cancer have been disappointing. Prostate cancer doctors have not been part of the excitement spreading through the cancer community like a “Mexican wave.”
Prostate cancer has not featured significantly in the cancer immunotherapy news recently, but that’s not to say there is not a lot going on. The phase 3 trial results of ipilimumab (a checkpoint inhibitor of CTLA-4) in the pre-chemotherapy setting of advanced prostate cancer (NCT01057810) are expected soon and there is also the eagerly awaited phase 3 trial of the PROSTVAC vaccine (NCT01322490).
At ASCO 2015, BSB interviewed Dr James L. Gulley, MD, PhD Chief of the Genitourinary Malignancies Branch and Director of the Medical Oncology Service at the National Cancer Institute (pictured above).
He talked about some of the cancer vaccine work he has done as part of the CRADA (Cooperative Research and Development Agreement) between the NCI and Bavarian Nordic, as well as strategies to help immunotherapy work in those tumors such as prostate cancer that are non-inflamed, where there may be an insufficient immune response for checkpoint inhibitors to work effectively.
Readers may recall we interviewed him at ASCO GU earlier year, “How to make non-immunogenic cancer sensitive to checkpoint inhibitors.” His outstanding work could shape the future of prostate cancer immunotherapy.
This post also includes additional ASCO 2015 commentary on from Dr Oliver Sartor, Professor of Cancer Research at Tulane University, who shared his perspective on the ipilimumab and PROSTVAC phase 3 prostate cancer trials that are due to readout soon.
Subscribers can login below to read more, or you can purchase access.
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).
To learn more about the latest insights on soft tissue sarcoma and GIST, you can log in or sign up in the box below.
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:
To learn more about our insights, subscribers can log-in or you can sign up in the box below.
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.
To learn more about our insights, you can sign up or log-in in the box below.
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.
To learn more about our insights on this important topic, you can sign in or sign up in the box below.
Chicago – it’s Monday at ASCO 2015, with a full day of symposia, oral abstracts and posters here in Chicago.
Yesterday in the Plenary Session here at ASCO, Dr Jedd Wolchok (Memorial Sloan Kettering Cancer Center) presented the results of the Checkmate 067 trial (LBA1) – the results of a phase III trial of nivolumab (NIVO) alone combined with ipilimumab (IPI) versus IPI alone in treatment naive patients with advanced melanoma. You can read more about this in our ASCO Day 3 highlights.
Dr Wolchok is pictured below, prior to presenting at the ASCO 2015 press briefing.
Checkpoint inhibitors have been a real buzz at this meeting, but with the realization that they are not going to work in all patients, and other treatments are not going away… for all the promise there’s still a lot of work to do optimize cancer immunotherapy.
There’s also been a lot of talk at ASCO about PD-L1 as a biomarker, and if you haven’t already done so, do check-out Episode 2 of the Novel Targets podcast (The Immune Biomarker Show) that touches upon many of the key issues.
If you haven’t already done so, do check out yesterday’s post on the metastatic lung cancer session, including the AZD9291 vs. rociletinib race to market in T790M, because there was some interesting new data presented that will likely have an impact today.
What’s hot on Monday at ASCO 2015? This will be the last of our daily posts from ASCO 2015. Subs can login to read our highlights as the day progresses. We’ll update schedule permitting.
Chicago – the cancer immunotherapy poster session yesterday morning was “mobbed,” that is the only word to describe it. I have never seen such a crowded poster session at any medical meeting before. It speaks to the huge interest in this growing field.
It’s also a reflection that insights into the future direction of the field will be found in posters about preclinical and early work, rather than in oral presentations that reflect strategic decisions made a long time earlier.
We know checkpoint inhibitors work in many cancers, and a few more have been added to the list at this meeting. While that’s interesting, the real question is how do we increase the response rate and also get them to work in non-immunogenic tumors?
Yesterday in the poster session at ASCO, there was a poster that caught our attention on one approach that may achieve this. We briefly wrote about it in the ASCO Day 2 blog.
Also of note yesterday was that the new generic name for the PD-L1 checkpoint inhibitor from Roche/Genentech. MPDL3280A is now atezolizumab. A few presenters stumbled over the pronunciation, it was so new…… and all the z’s add to the trickiness!
As to what Day 3 at ASCO holds, we’ll be updating this blog during the day as our schedule permits.
Subscribers can login below or you can purchase access.
Chicago – after an evening of beer and networking at the unofficial ASCO15 Tweetup, the ASCO annual meeting, like a checkpoint inhibitor combination, releases the break and steps on the gas: the main data presentations start today. It’s “super saturday” at ASCO15.
Yesterday, the press had a preview of some of the cancer immunotherapy data to be presented this morning – we’ve shared our preliminary thoughts on this in yesterday’s ASCO15 Day 1 Cancer Immunotherapy post.
So what’s hot at #ASCO15 today?
We’ll be doing a rolling post throughout the day – when the opportunity presents we’ll provide some topline thoughts on sessions we’ve been to.
If you are here at ASCO, one #ImmunOnc presentation to watch out for this morning is the David A Karnofsky memorial award and lecture being given by Suzanne L. Topalian, MD in the main plenary hall (N Hall B1) at 11am.
From the recent presentations we’ve heard from her at AACR and AAI, her lecture entitled, “PD-1 Pathway Blockade – a Common Denominator for Cancer Therapy” should definitely worth listening to!
Subscribers can login below to read our updates throughout the day.
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.
Subscribers can login below to read more or you can purchase access by clicking on the blue icon.