Biotech Strategy Blog

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

Posts tagged ‘Checkpoint Combinations’

What does atezolizumab TNBC data presented at AACR17 tell us about breast cancer immunotherapy?

Prof Peter Schmid

Prof Peter Schmid, Barts Cancer Institute

Peter Schmid FRCP, MD, PhD is Professor of Cancer Medicine at Barts Cancer Institute in London, where he is also Clinical Director of the St. Bartholomew’s Breast Cancer Centre and leads the cancer immunotherapy group.

One of my favourite interview quotes of all time comes from his fellow Barts cancer researcher, Professor Tom Powles who told BSB about the results he had seen with the anti PD-L1 monoclonal antibody, atezolizumab (Roche/Genentech) in urothelial bladder cancer:

“I have a cohort of men and women now, who had been told they have 6 months to live who are now two or three years down the line.”

This encapsulates the hope that cancer immunotherapy offers. (See post: Atezolizumab PDL1 Checkpoint Inhibitor will change Bladder Cancer Treatment).

Barts Cancer Institute in the City of London is pioneering research into cancer immunotherapy in both the clinical and preclinical arenas.

Readers may recall we previously interviewed Professor Fran Balkwill last year about the work her research group is doing into modelling the tumour microenvironment. This is an exciting area that we can expect to hear more about. (See post: Modelling the Tumor Microenvironment).

So where are we with breast cancer immunotherapy in triple negative breast cancer (TNBC)?

It’s now two years since the first atezolizumab TNBC clinical trial data was presented by Dr Leisha Emens (Johns Hopkins) at the 2015 annual meeting of the American Association for Cancer Research (AACR), how time flies!  (See post: Checkpoint Inhibitor Data Rocks AACR 2015)

As regular readers know, we like to follow stories over time and report on how the longitudinal data progresses.

Professor Peter Schmid kindly spoke to BSB at the 2017 AACR annual meeting in Washington DC where he presented more mature clinical trial data for the PD-L1 checkpoint inhibitor, atezolizumab, as a single agent in TNBC.

What are the key take homes from this data, and the ongoing challenges and opportunities in TNBC?  Prof Schmid shared his unique perspective.

This is the first in a series of expert interviews from #AACR17.

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5 Important and Emerging Trends from ASCO 2016

We have selected five key strategic trends that are emerging that will be critical to follow, understand, and even implement if you are on the coal-face of clinical research and new product development.

ASCO16 Chicago 5We aren’t talking about financial things such as cost toxicity, or even how doctors should be paid, but meaty scientific aspects that we need to watch out for. If we are going to improve on cancer research and R&D in the future, these issues will be important.

For companies and academic researchers alike, there is much to learn from the tsunami of data that hit this week if you have a keen interest in the field and a bent for making sense of patterns out of an amorphous mass of data.

Not paying attention to evolution in clinical development can mean the difference between being in the winners circle, on the outside looking in, or falling way behind your competitors. Playing catch up is never anyone’s idea of fun in this market – oncology moves at a lightning fast pace compared to many other therapy areas.

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Are checkpoints playing with fire?

Honolulu: Yesterday we learnt the sad news that Dr Holbrook Kohrt (pictured) had died.

Dr Holbrook Kohrt He was a Stanford hematologist/oncologist and rising star in the cancer immunotherapy field. Our thoughts go out to his family and friends.

I had the privilege to interview him last May at the Immunology 2015 meeting in New Orleans. One area of Dr Kohrt’s research was in combination immunotherapies, and how we can optimize efficacy, while avoiding significant immune adverse events.

So are checkpoints playing with fire when given in combination?

That was one of the provocative questions to come out of a scientific session entitled, “Fast Cars and No Brakes: Autologous Stem Cell Transplantation as a platform for Novel Immunotherapies” at the BMT Tandem meeting in Hawaii last weekend. The session, chaired by Miguel-Angel Perales (@DrMiguelPerales) from Memorial Sloan Kettering Cancer Center, was both informative and interesting.

All the presentations were excellent, but one by Philippe Armand from the Dana-Farber Cancer Institute in Boston, “Checkpoint Blockade in SCT, Data & Hope, Promise & Peril” stood out for me. Dr Armand discussed checkpoint data pre and post stem cell transplantation and offered a perspective I had not heard before.

One of the provocative questions it raised was could checkpoints be playing with fire in some patients? Dr Armand kindly spoke with BSB after his talk.

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Checkpoint inhibition: targeting TIM-3

Over the last couple of years we have heard much about targeting various checkpoints that exert an inhibitory effect on the immune system and the T cells, in particular.  The main targets where we have a growing body of evidence to date are CTLA-4, PD-1 and PD-L1, but there are others including LAG-3, TIM-3, ICOS etc.

Earlier this year at AACR, we saw new evidence that combining two checkpoints (anti-CTLA4 and anti-PD1) was superior to monotherapy in metastatic melanoma, albeit with a concomitant increase in toxicities.

What about the other inhibitory signals though?  Are they bystanders, much like passenger mutations that have little effect, or do they matter, at least in some tumor types?  If so, which ones?

We took a look at some of the emerging data associated with targeting TIM-3 – the results may well surprise some observers.

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