Durvalumab

Next, uh, Destiny Long O three was a multi-arm study evaluating T-DXd alone, so sort of confirmation of what was found in, um, um, Destiny Long O one and in combination with other treatments.

And the first objective was actually to replace, um, pemetrexed and cisplat-- and pemetrexed in, um, patients with HER2 overexpressing non-small cell lung cancer as a first-line treatment in combination with platinum and, um, immunotherapies, in this case durvalumab.

That s- uh, that study did not support further investigation i- in the combination with duvelumab and cisplatin or duvelumab and carboplatin because of safety concerns.

However, there was clinical benefit with T-DXd monotherapy, uh, uh, in arm 1d, and that is what you can, uh, appreciate from this waterfall plot.

So you can see here, stage 1, 2, 3, limited stage encompassed by a radiation field, important to do staging, PET-CT, brain MRI, and a randomized after completion of chemotherapy and radiation study.

to durvalumab or ether placebo.

And you can see here the radiation was ether daily or twice a day, BID.

So that's important to know.

Uh, we also have the AVANZAR study, which I'm hoping we'll get a readout relatively soon.

That's looking at durvalumab, datopotamab, and platinum versus your KINO-one-eight-nine.

And importantly, there they are gonna look at a biomarker positive select group.

That biomarker is an AI biomarker using digital path, and so we'll need to change our workflows if we use something like that.

This is the first time that they're, they're having small cell lung cancer.

The only person missing the holiday is us, right? And, uh, it's translating a survival benefit.

And so we explain to the patients, "Look, we're going to start with three drugs, platinum, etoposide, immunotherapy, either durvalumab or atezo.

We're going to start with three drugs.

Depending on the study, it had to be at least six months or 12 months since they completed it.

GY018, which looked at pembrolizumab, and DuoE, which looked at durvalumab.

They had to have at least a 12-month chemo-free interval.

And then the Ruby study, which looked at dostarlamab, they had to have six months prior from their last chemotherapy.

So she was actually enrolled in the DUO trial in November, 2019, and she received six cycles of carboplatin plus paclitaxel plus bevacizumab plus durvalumab or placebo.

That was the randomized study.

And after the chemotherapy, she received 22 cycles of Bevacizumab plus Durvalumab placebo, plus Olaparib placebo, according to the study.

She relapsed.

The first relapse was in May.

Now, the question is, do we have to stop treatment at two years? Should we continue the treatment at two years? While the EV302 trial had a kind of stop of EV at two years and continue with pembrolizumab, we also have the NIL trial that has not been read out yet and it's not reported.

But just to remind our audience that this is a trial where patients were randomized to cisplatin gemcitab and durvalumab or cisplatin gemcitab and durvalumab tremolimumab And the control was this platinum gemcitabine.

In that specific trial, patients had a set number of cycles of platinum-based therapy.

And then durvalumab or durvalumab tremolimumab was continued indefinitely.

So actually, I have a patient that we're now year five of single agent durvalumab.

And actually, that individual... at the time of metastasis, had liver meds and bone meds and has CR.

And we don't, we are not stopping treatment.