ASCO and PD1, PDL1

A lot of you have been following the news about the new drugs that block PD1 or PDL1, and you may have seen that new data were reported yesterday at ASCO.  I thought you might like a bit of an update.

For months researchers have been talking about these drugs, with some optimism.  

WHAT ARE THESE DRUGS?

A lot of you have been following the news about the new drugs that block PD1 or PDL1, and you may have seen that new data were reported yesterday at ASCO.  I thought you might like a bit of an update.

For months researchers have been talking about these drugs, with some optimism.  

WHAT ARE THESE DRUGS?

I am not a scientist, but here is my understanding.  Our immune system has a lot of different components, including T-cells.  These cells should attack tumor cells and kill them before they are able to grow, divide, and move around the body.  But if T-cells were active all the time they would also attack good cells, resulting in auto-immune disease.  So the body has several mechanisms to stop T-cells from functioning.  One of those mechanisms involves a compound called CTLA4, and Yervoy (ipi) works by blocking the activity of that compound.  In essence, Yervoy takes the brakes off the immune system.

PD-1, which stands for Programmed Death 1, is another compound in the CTLA4 family.  These new drugs block PD1, just as Yervoy blocks CTLA4.  Four companies have anti-PD1 drugs in development, but BMS is further along in the process than the others, with Merck a close second.  

PD-1 has a counterpart on some tumor cells called PDL1, or PD-1 ligand.  When PDL-1 interacts with T-cells it shuts them down, making them ineffective.  So at least two companies, BMS and Genentech, are working on drugs that block PDL-1.  

WHAT IS THE DATA SO FAR?

The data yesterday showed that in a relatively small study, anti PD-1 has strong activity in metastatic melanoma.  Response rates in a group of studies ranged from 19% to 40%, with relatively minor side effects.  While these are very exciting numbers, it is still early days.  Several other compounds have shown good results in small studies, only to be less effective in larger groups.

Studies of anti-PDL1 are less mature, but are also showing some good responses.  Part of the problem here is that we know of two different ligands for PD-1, called PDL-1 and PDL-2.  If you block one, the other may still be able to shut down the T-cells.  Also, it may well be that other PD1 ligands exist that have not yet been discovered.

WHERE ARE THE STUDIES NOW?

Both BMS and Merck are moving forward with additional studies, including a number of specific trials for people who have been on ipi, people with ocular melanoma, etc.  So we should be see quite a few more slots over the next few months.  

Researchers have been concerned that the companies are moving too slowly in developing these drugs.  The MRF Breakthrough Consortium formally contacted the companies with this concern over a year ago, with the result that more melanoma slots were made available.  In fact out of several different cancers studied with these drugs, melanoma was second in number of patients enrolled.

I have been in contact with the companies and have expressed this concern as well, so they know that patients are paying very close attention to this.  The intention is the keep the pressure on, and at some point I may ask people from this board to contact the companies to help with this pressure.

THE BOTTOM LINE

I can tell you that hallway conversations at ASCO are all about these drugs.  Some feel they will become the standard of care over the next few years. Some even think we may see very high response rates, and even cures from these drugs.  One person said, "We may be able to cure 40% of melanomas within a few years."  I think this is too bold, given the early state of the data.  A lot can change between where we are now and where we need to be.  Having said that, it is great to feel the enthusiasm and energy around this.  I remain convinced that we live in a time of real hope for melanoma, and equally convinced that we must keep pushing as hard as possible to move the research forward as quickly as possible.

Tim–MRF