Tyrosine kinase inhibitor

Mine is in a tablet form.

They're called TKIs.

I was told before I think 2000 that if you got the cancer I have, it was pretty much a death sentence.

But healthcare has grew and it's now at a point where I just have to take a tablet every day for the rest of my life.

and i think you know for for instance cosmic 313 which was ip nevo cabo right one of these very small insignificant successes of that trial was that the pd rate was brought down by integrating a tki right so here we see that again the the upfront progression rate for the triplet is, quote, only 4.8%, which obviously is much better than what we see.

Does that mean anything to you? Does that sort of strengthen your desire to do triplets? I mean, all the arms got a

TKI.

All the arms got Len, right? So when you introduce a TKI up front, you have better disease control.

Whether you give two or three drugs, I don't know that it matters.

I mean, they're almost identical.

I think they're 4% to 5% across all the arms.

Okay.

And I'm still continuing on the immunology-based stream as well, which is the immune response to antibody therapies and now antibody drug conjugates as well.

So, yeah, you can definitely follow a line through from the original PhD where this HER2 targeting TKI, lopatinib, we were looking at as a possible modulator of multidrug resistance.

Then that was brought through into the postdoc work, which was, as you said, was looking at the immune response to trastuzumab and how lopatinib could affect that.

That was back around 2011, 2012.

Some of our oldest being trastuzumab or single epitope monoclonal antibodies.

But we also have small molecule TKIs.

We have antibody drug conjugates such as TDXD.

And most recently, we have bispecific antibodies, for example, Xanadatnap.

Great.

And so for our listeners who are not oncologists, can you briefly explain why tyrosine kinase inhibitors or TKIs, especially those with anti-VEGF, matters to us, to retina specialists? Maybe just describe briefly how they work and why it matters to our community.

Yeah.

So tyrosine kinase inhibitors are, as you mentioned, oral cancer drugs that can block VEGF like receptors, but they have sort of multimodal agents.

I mean, for me, I think, you know, as a retina specialist, I'm often so focused on the eye that I forget about some of the systemic impacts that, you know, treatments that my patients might be on, especially in the field of oncology where it feels like there's constantly new treatments sort of available.

But it's really good, you know, to keep in mind that our patients are increasingly on therapies like this and what risks they might have for the eye.

And now, are all these TKIs targeted to the VEGF receptor? Are there other agents that target toward other tyrosine kinases that are not VEGF receptors?

Yeah.

We've really seen an explosion in the treatment landscape for patients with HER2 mutant non-small cell lung cancer, focusing on the US and EU.

I think what's really important here is if you look at the initial TDXD trials starting in 2020 to the approval of TDXD initially in 2022, and similarly from the initial trials of both zonguertinib and sevabertinib, the HER2 TKIs, only a couple of years between those trials starting and approval.

So we've really seen the pace of discovery here really rapidly evolving and improving, and the time of translation to the clinic also rapidly changing.

So we now, as we'll hear from Dr. Zuguzagoysha, have multiple approved options for these patients.

These are targetable biomarkers, and now we have novel treatment options, so really important to recognize these as a unique entity to offer these therapies to our patients.

So if we take that somewhat negative slide that I had before about all the challenges we faced, I'm excited to say that this is now looking different.

We now have good treatment options, targeted therapies for our patients with HER2 mutant lung cancer, including the HER2 TKIs, Zongertinib and Cevabertinib, approved in many parts of the world, although we acknowledge not all, and we hope to see access to these therapies expand.

We see actually now both of these TKIs in the United States, as of just last week, approved for frontline use.