Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘PD-L1 MPDL3280A’

Top 10 immunotherapy studies with checkpoint blockade at ASCO 2015

As we wrap up our AACR coverage, I can’t believe it’s already time to discuss the annual American Society of Clinical Oncology (ASCO) meeting already – it seems to come around way too fast.

Over the last few years, we’ve reported on the rapid and impressive rise of innate, adoptive and adaptive immunotherapies in cancer research and wondered how long it would take before we see such data presented in the plenary session.  That actually happens this year… finally!

Fireworks River Thames

A checkpoint trial makes the ASCO 2015 Plenary!

It does look like 2015 is the year that checkpoint inhibitors cannot be ignored for plenary selection with the wealth at data available at first AACR and now ASCO emerging.

This is no bad thing, especially given these drugs can affect the long tail of survival and are really starting to impact the dismal 5-year survival rates in metastatic melanoma and non-small cell lung cancer (NSCLC).

Beyond those two tumour types, what else can we expect to see and how is the data likely to shape up?  We took a look at the abstracts available based on the titles only, the actual abstracts themselves come out next week.

What did we find?

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The Science of PD1 PDL1 Cancer Immunotherapy

Nature Cover Checkpoint InhibitorsIn 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:

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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.

Happy Thanksgiving!

Subscribers can login to read more detail about all five Nature Letters, and their implications for the emerging field of immuno-oncology.

Tower of London Field of Poppies

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ASCO GU 2014 Optimal targeting of anti PD-1 and PD-L1 therapies in renal cancer

We’ve been hearing and writing about a substantial amount of news and information on various immuno-oncology developments over the last year, especially in metastatic melanoma and lung cancer, but despite renal cell cancer (RCC) being a proven immune-sensitive disease with known PD-L1 expression, it seems to be the poor cousin to the other two tumour types given the lag in data and relative media attention.

There’s actually quite a lot going on in this disease though, from biomarker work to phase I to III trials that are either ongoing or just started accruing.

We should be hearing much more about the role of anti-PD–1 and PD-L1 antibodies in RCC over the next couple of years, including data from some large randomised controlled trials, but what’s the current state of play?

With that in mind, I was delighted to catch up with David McDermott’s (DFCI) in-depth presentation at ASCO GU in San Francisco over the weekend.  It’s always unfortunate when an interesting talk is left for the final presentation on the last day of a conference, as only a few diehards will be there to catch it!  It was a well thought out discussion though and he covered a lot of interesting ground in this space.

Agents mentioned:
ipilimumab, nivolumab, MK–3475, MPDL3280A, LAG–3, TIM–3, PD-L2, IL–2, sunitinib, everolimus, bevacizumab

Companies mentioned:
BMS, Roche/Genentech, Merck, GSK, Novartis, Pfizer

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What to watch for at San Antonio Breast Cancer Symposium

Whew, having just finished the American Society of Hematology (ASH) meeting, we run on to the breast cancer symposium in San Antonio (SABCS), making for a very busy week of data deluge!  Our Post ASH analysis will also run concurrently for a few days.

There are also a number of interesting areas to look out for in terms of interesting breast cancer developments.

Premium subscribers can find out more about the following below:

Companies: Roche, GSK, AbbVie, AstraZeneca, Novartis, Lilly
Drugs: Herceptin, Avastin, Perjeta, Tykerb, veliparib, olaparib, BKM120, ramucirumab, PD-1, PD-L1

Here’s a quick preview of some of the landmark data emerging from this conference, some positive, some negative.

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Preview of 2013 European Cancer Congress in Amsterdam

Last week saw the release of the majority of the abstracts for the 2013 European Cancer Congress that takes place at the RAI conference center in Amsterdam from September 27 to October 1st (Twitter hashtag #ECC2013). Not yet available are the late-breakers and those abstracts included in the media press conference program.

ECCO Congress BannerThe European Cancer Congress is the euro equivalent of the American Society of Clinical Oncology (ASCO) annual meeting and is organized in alternate years by the European CanCer Organization (ECCO) and European Society for Medical Oncology (ESMO). This year it’s the turn of ECCO who ran an excellent meeting in Stockholm in 2011.

Scan the QR code to download the ECCO Amsterdam Cancer Congress AppHere are links to the #ECC2013 abstracts and searchable Congress programme.

There is also an ECCO App that’s well worth downloading. It offers the meeting program with links to abstracts, as well as floor plans and can also be used to follow the #ECC2013 conversation on Twitter.

ECCO have made it as easy as possible for people to download the app, just scan the QR code and it will take you to the download page for your phone (iPhone or Android).

ECCO have also published their list of abstracts not to be missed – a few on their list that stand out for me include:

Breast Cancer:

1859 – PI3KCA mutations and correlation with pCR in the NeoALTTO trial (BIG 01-06)

Prostate Cancer:

2853: An open-label phase 1/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (CRPC).

2854: The effects of enzalutamide (ENZA) in combination with abiraterone acetate (AA) in patients with bone metastatic castration resistant prostate cancer (mCRPC)

Lung Cancer:

3401:  Updated results of a first-in-human dose finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies.

3408: Clinical activity, safety and biomarkers of PD-L1 blockade in non-small cell lung cancer (NSCLC): additional analyses from a clinical study of the engineered antibody MPDL3280A (anti-PDL1)

Ovarian Cancer:

In the plenary Presidential sessions several of the presentations focus on ovarian cancer with results being report for the following trials: ICON6 (cediranib), AURELIA (bevacizumab), ICON7 (bevacizumab).

As always I will be mining the posters for gems, and attending as many of the scientific and educational sessions as I can.

Regretably, to offset costs, I will be introducing a paywall for most of the conference coverage from ECC2013 in Amsterdam. In this respect I’m following leading publications such as The New York Times and The Wall Street Journal. I will be providing some additional commentary to those who subscribe to BSB email alerts so do sign up if you have not already done so.

I hope to see you in Amsterdam!

Update Sept 17: Preview of Late Breaking Abstracts and PI3K Abstracts

Sally Church (@MaverickNY) has published her ECCO 2013 preview on Pharma Strategy Blog (free access). Abstracts that caught Sally’s attention included those on T-DM1, everolimus, FLT1 gene varation in NSCLC and evaluation of GDC-0032, a next generation PI3K inhibitor.

Data on GDC-0032 and its early promise in breast cancer was presented at the AACR annual meeting earlier this year.

ASCO 2013 Preview Video

In her annual preview video of what’s hot at ASCO 2013, Sally Church (@Maverickny) discusses several therapeutic areas with new data at the meeting including:

  • Immunotherapy (PD-1, PD-L1, CTLA-4)
  • CLL (GA-101, idelalisib, IPI-145)
  • Breast Cancer (palbociclib, PF-05280014)
  • Lung Cancer (LDK-378, AP26113)
  • Pancreatic Cancer (Abraxane, TH-302)

This video was originally published on Pharma Strategy Blog and includes an edited mechanism of action (MOA) for PD-L1 (courtesy of Roche/Genentech). Several people have since remarked it’s the first time they fully understood what “upregulation” meant.

If you missed the video, it’s well worth watching again in the run up to ASCO 2014.

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