And here in Part 2, we start out with BRCA positive scenarios and a report on the KeyLink 009 study evaluating maintenance treatment for metastatic triple negative breast cancer comparing pembrolizumab plus olaparib versus continued pembrolizumab plus chemotherapy after initial clinical benefit from first-line pembrolizumab and chemotherapy.

When I think about the first-line treatment of triple negative breast cancer in general, obviously BRCA1 is important.

We know that it's associated with differences in response to different types of standard cytotoxic therapy, right? TNT study, we see higher response rates with platinum-based treatment than with taxins, for example.

So that was the basis for some potential clinical utility of BRCA status, even outside of a PARP inhibitor.

But In the first line setting, I think the most important thing to consider first is the PD-L1 status, because as we talked about, you know, from the outset, pembrolizumab can transform the outcomes for a small group of patients.

So we don't know how to identify those patients up front beyond the fact that, of course, they're PD-L1 positive.

And so having immunotherapy in the first-line setting for PD-L1-positive disease, I think, is a strategy that I prefer because of that possibility of a durable, complete response.

Can you talk a little bit about the types of immune adverse events that you're seeing in patients with triple negative breast cancer, what they looked at in this study, and in general, what we know about the correlation, if any, between immune complications and treatment benefit?

And here in part two, we start out with BRCA positive scenarios and a report on the KeyLink 009 study evaluating maintenance treatment for metastatic triple negative breast cancer comparing pembrolizumab plus olaparib versus continued pembrolizumab plus chemotherapy after initial clinical benefit from first-line pembrolizumab and chemotherapy.

when I think about the first line treatment of triple negative breast cancer in general, obviously BRCA1 is important.

We know that it's associated with differences in response to different types of standard cytotoxic therapy, right? TNT study, we see higher response rates with platinum-based treatment than with taxins, for example.

So that was the basis for, you know, some potential clinical utility of BRCA status, even outside of a PARP inhibitor.

But In the first-line setting, I think the most important thing to consider first is the PD-L1 status.

Because as we talked about, you know, from the outset, pembrolizumab can transform the outcomes for a small group of patients.

So we don't know how to identify those patients up front beyond the fact that, of course, they're PD-L1 positive.

Can you talk a little bit about the types of immune adverse events that you're seeing in patients with triple negative breast cancer, what they looked at in this study, and in general, what we know about the correlation, if any, between immune complications and treatment benefit?

metastatic breast cancer.

So along with the understanding that these TROP2 ADCs have more activity than chemotherapy, we've had, again, these trials that have looked at combining that strategy of TROP2 ADC and immunotherapy versus the standard of care Keno 355 regimen of pembrolizumab and chemotherapy.

So, again, this is a bit different from those other studies, which are kind of bringing an established monotherapy strategy into the first-line setting.

In the case of SG, this is now combining SG with PEMBRO.

So, you know, it's a new therapeutic combination, not just moving SG as monotherapy into the first-line setting.

So, we've seen the results of ASCENTO4, which was precisely that combination of sasituzumab given in the standard way combined with pembrolizumab.

given in the standard way, versus the Keynote 355 regimen in the Keynote 355 eligible population for sign metastatic disease, treatment-free interval of greater than six months, who are PD-L1 positive.

But just in general, what we know about the tolerability issues with both of these agents, and how to prevent and manage them, and also the difference in the treatment schedule with these agents.

incurable metastatic breast cancer.

So, you know, along with the understanding that these TROP2 ADCs have more activity than chemotherapy, we've had, again, these trials that have looked at combining that strategy of TROP2 ADC and immunotherapy versus the standard of care, you know, 355 regimen of pembrolizumab and chemotherapy.

So, again, this is a bit different from those other studies, which are kind of bringing an established monotherapy strategy into the first line setting.

In the case of SG, this is now combining SG with PEMBRO.

So, you know, it's a new therapeutic combination, not just moving SG as monotherapy into the first line setting.

So we've seen the results of Ascento4, which was precisely that combination of sasituzumab given in the standard way combined with pembrolizumab given in the standard way versus the Keno355 regimen in the Keno355 eligible population for sign metastatic disease, treatment-free interval of greater than six months who are PD-L1 positive.

And we've now, again, seen these results, including the primary endpoint to progression-free survival, where we see improvement in PFS with the combination of SG and PEMBRO versus chemo and PEMBRO.

But just in general, what we know about the tolerability issues with both of these agents and how to prevent and manage them, and also the difference in the treatment schedule with these agents.

incurable metastatic breast cancer.

So, you know, along with the understanding that these TROP2 ADCs have more activity than chemotherapy, we've had, again, these trials that have looked at combining that strategy of TROP2 ADC and immunotherapy versus the standard of care, you know, 355 regimen of pembrolizumab and chemotherapy.

So, again, this is a bit different from those other studies, which are kind of bringing an established monotherapy strategy into the first line setting.

In the case of SG, this is now combining SG with PEMBRO.

So, you know, it's a new therapeutic combination, not just moving SG as monotherapy into the first line setting.

So we've seen the results of Ascento4, which was precisely that combination of sasituzumab given in the standard way combined with pembrolizumab given in the standard way versus the Keno355 regimen in the Keno355 eligible population for sign metastatic disease, treatment-free interval of greater than six months who are PD-L1 positive.

And we've now, again, seen these results, including the primary endpoint to progression-free survival, where we see improvement in PFS with the combination of SG and PEMBRO versus chemo and PEMBRO.

But just in general, what we know about the tolerability issues with both of these agents and how to prevent and manage them, and also the difference in the treatment schedule with these agents.