KRAS

I had tears too because I was unfortunately thinking of all the people.

that I wondered could have benefited from it, from the new drug that they were presenting, the Teroxanracib KRAS inhibitor.

But I said that to a few family members and to a few people on our board about that it was a bittersweet moment to be in the room.

And what was interesting is that the people that I knew who had lost people were more hopeful than they were sad about this announcement because all they wanted was future people not to have what happened to their loved one happen.

Sure.

So the new drug is called Deroxanracib, and it is a pan-RAS inhibitor.

And what does that mean? RAS, or specifically KRAS, is a protein that is present in all pancreatic cancer, almost all pancreatic cancers.

And it's a gene that causes the cancer to grow.

These patients are four times more likely to have a target mutation.

So the most common mutations are ALK fusions, EGFRs, and KRAS G12D, as in David.

So they're genomically different.

It's estimated that around 66% of young patients have a target mutation.

So I think the numbers are going to keep going up.

I have a 19-year-old with ROS1 disease.

I have a 23-year-old with KRAS G12D.

And they're just getting younger.

Yeah, and it may be that combining with other agents as opposed to agents that hit other forms of RAS might be the more fruitful path because, as John mentioned, some of these other forms of RAS are in normal cells, and that's where the side effects come from.

And I think the mechanisms of resistance is a really important thing to discuss as well, because originally it was thought, and I think Revolution Medicines had said that a pan-RAS should give you longer efficacy, more durable, because with the early KRAS inhibitors, the G12C inhibitors, Other acquired resistance mechanisms tended to be other RAS mutations, and the idea was if you hit RAS broadly, you won't have those resistance mechanisms.

What we've seen preclinically is that the tricomplex or on-only inhibitors bring a whole other host of resistance mechanisms that don't apply to our drug, and really... we know that cancer is not going to take any drug lying down.

It's just going to find other ways around it.

But there's many other opportunities for RAS inhibition or targeting the RAS pathway.

Kind of what's like the broad potential you see for RAS inhibition in these other types of cancers?

It's been estimated that there are more than 60,000 new patients a year in the U.S. alone that have a cancer that's driven by the KRAS G12D mutation.

Again, it's the most common KRAS mutation in human cancer, about 40% of pancreatic, but about 15% of colorectal, about 5% of lung cancer.

Good afternoon, everyone.

I'm Neil Love from Research to Practice, and welcome to Where We Are and Where We're Heading, Targeting KRAS G12C and Non-Small Cell Lung Cancer.

We have a great faculty tonight, Professor Solange Peters from the Lausanne University Hospital in Lausanne, Switzerland, and Dr. Josh Sabari from the Perlmutter Cancer Center and the NYU Grossman School of Medicine in New York City.

Tonight, we're going to talk about KRAS G12C inhibitors, and as I started to explore this, I got very, very excited, and I'm super excited to talk about this tonight.

We will be discussing the use of non-approved agents and regimens, so check out the package inserts for more.

Here's where we're heading.

I'm going to start out and provide a little bit of a background to what we're going to talk about tonight.

Then we'll get into the biology of KRAS-G12C and the inhibitors there, the available and approved agents, and particularly use in the second line.

And I spoke to Dr. Ajaz Khan, Chief Medical Oncology at City of Hope Cancer Center, about this.

What we really know about pancreatic cancer is that it grows based upon this gene called KRAS.

And so basically what it works on is deactivating or basically trying to shut down that cancer gene and allow it to make other cancer cells and cancer proteins grow.

Think of that genetic mutation on his K-Rez as an on and off switch.

It's going to be the first oral drug that's been approved in pancreatic cancer in more than 14 years.

It is the first targeted drug specifically for pancreatic cancer that we've had ever.

Anyone with advanced pancreatic cancer that has a KRAS mutation that can't receive chemotherapy or tolerate chemotherapy could get this drug.

And the FDA's approval is significant because this isn't just simply another chemotherapy drug.