So, Dr. Sands, we went through this patient case, gave background, but based on this patient's presentation, how would you select among the current NCCN preferred first-line treatment options for extensive stage small cell lung cancer? And what clinical or trial-based factors would influence your choice of induction and maintenance therapy?

Well, with some of the recent big advances in the field is the incorporation of the PD-L1 inhibitors in the first-line setting.

Incorporation of atezolizumab or dervalumab as current standards right now with platinum atoposide, overwhelmingly important.

It's a subset of individuals that really benefit from these PD-L1 inhibitors, but nothing else works like it.

So these PD-L1 inhibitors, when they work, I have people that are seven years or longer from the time of their initial diagnosis of metastatic small cell lung cancer that have ongoing disease control at this point years off of treatment.

And so I think these PD-L1 inhibitors are actually curing some people of their incurable disease, which makes them overwhelmingly important for every patient to get as part of their treatment, with the exception of those in whom it's obviously contraindicated, like certain transplant, organ transplant, for example, or severe autoimmune comorbidities, those types of things.

But broadly speaking, everybody should get these.

So Dr. Sands, given this patient's progression after first-line therapy, how would you think about selecting among the NCCN preferred subsequent systemic therapy options for extensive stage small cell lung cancer? And what clinical factors would help guide your decision-making process?

Can you explain clearly for people the differences in staging for small cell lung cancer?

Although I don't know the specifics of your friend, if someone's getting radiation overwhelmingly, very commonly, they'd get chemotherapy with that and then immunotherapy after that.

But that's important to our staging discussion too.

So staging is, there is stage one, two, three, four, like other cancers, but we often talk about small cell lung cancer as limited stage and extensive stage.

Now, that being said, the caveat is with stage one, which is generally just a nodule.

no lymph nodes involved, a nodule in the lung that's not a large one.

The treatment of that can be surgery.

When someone is newly diagnosed with small cell lung cancer, what are the most important steps you would advise when they're considering starting treatment?

Can you talk a little bit about, uh, kind of what T-cell engagers are, what DLL-3 is, um, where it's expressed in addition to small cell cancer, and, uh, what, uh, how tarlatamab works?

works?Yeah, DLL3 is very common in small cell lung cancer.

In the tarlatamab studies, it's been about ninety-five percent of the tumors of those individuals enrolled to the tarlatamab arms.

So very common in small cell.

Uh, but it is also present in other neuroendocrine carcinomas.

And so, uh, tarlatamab is a bispecific T-cell engager, binds CD3 on T-cells, binds DLL3 on small cell lung cancer, and pulls them together, creating an immune response.

Now, tarlatamab has really just been studied in small cell lung cancer, but obrixtimig, another bispecific T-cell engager, also to CD3 and DLL3, has enrolled broadly across other tumor types, including large cell neuroendocrine carcinoma, where low numbers but a reported seventy percent response rate, seven out of ten.

Uh, but can you talk a little bit more about B7H3, Jacob? Uh, uh, how much it's expressed, um, and what IDXD actually is, and what we know about it in terms of efficacy and tolerability?

Well, thanks everyone for joining.

My name is Jacob Sands.

I'm a thoracic medical oncologist at Dana-Farber Cancer Institute, where I lead our small cell lung cancer program.

I'm excited to talk about some of the advances over the last year in small cell lung cancer.

This is not comprehensive, but highlighting, uh, some of the different meaningful publications and data releases that we've seen.

So first of all, starting out in the limited-stage small cell lung cancer setting, we've seen two trials that were particularly important.

Can you talk a little bit about, uh, kinda what T-cell engagers are, what DLL-3 is, um, where it's expressed in addition to small cell cancer, and, uh, what, uh, how tarlatamab works?

works?Yeah, DLL3 is very common in small cell lung cancer.

In the tarlatamab studies, it's been about ninety-five percent of the tumors of those individuals enrolled to the tarlatamab arms.

So very common in small cell.

Uh, but it is also present in other neuroendocrine carcinomas.

And so, uh, tarlatamab is a bispecific T-cell engager, binds CD3 on T-cells, binds DLL3 on small cell lung cancer, and pulls them together, creating an immune response.

Now, tarlatamab has really just been studied in small cell lung cancer, but obrixtimig, another bispecific T-cell engager, also to CD3 and DLL3, has enrolled broadly across other tumor types, including large cell neuroendocrine carcinoma, where low numbers but a reported seventy percent response rate, seven out of ten.

Uh, but can you talk a little bit more about B7-H3, Jacob? Uh, uh, how much it's expressed, um, and what IDXD actually is, and what we know about it in terms of efficacy and tolerability?

Can you talk a little bit about, uh, kinda what T-cell engagers are, what DLL-3 is, um, where it's expressed in addition to small cell cancer, and, uh, what, uh, how tarlatamab works?

works?Yeah, DLL3 is very common in small cell lung cancer.

In the tarlatamab studies, it's been about ninety-five percent of the tumors of those individuals enrolled to the tarlatamab arms.

So very common in small cell.

Uh, but it is also present in other neuroendocrine carcinomas.

And so, uh, tarlatamab is a bispecific T-cell engager, binds CD3 on T-cells, binds DLL3 on small cell lung cancer, and pulls them together, creating an immune response.

Now, tarlatamab has really just been studied in small cell lung cancer, but obrixtimig, another bispecific T-cell engager, also to CD3 and DLL3, has enrolled broadly across other tumor types, including large cell neuroendocrine carcinoma, where low numbers but a reported seventy percent response rate, seven out of ten.

Uh, but can you talk a little bit more about B7-H3, Jacob? Uh, uh, how much it's expressed, um, and what IDXD actually is and what we know about it in terms of efficacy and tolerability.

Jacob, can you touch on the data here? And importantly, what's your practice around PCI? Who do you consider PCI for? And if so, what's the timings like in relationship to immunotherapy?

Yeah.

So I'll come back to the PCI.

That is a murkier question.

To start out with, the data that we have from ADRIATIC, so concurrent chemoradiation, platinum etoposide and radiation, then followed by two years of durvalumab.

That's-- The, the ADRIATIC study showed a seven-and-a-half month improvement in the median progression-free survival, 22-and-a-half month improvement in median overall survival.

These are astonishing numbers.

Right.