Hello, my name is Krista and I will be your conference facilitator today for Amgen's investor call from the European Society for Medical Oncology Congress 2026. All lines have been placed on mute to prevent any background noise. There will be a question and answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star then the number one on your telephone keypad. To withdraw your question, please press star one again. I would now like to introduce Casey Capparelli, Vice President, Investor Relations. Mr. Capparelli, you may-
Joining our call from ESMO here in Madrid. The slides that we'll be reviewing are now available on our Amgen IR website. Please see in the slides that accompany this presentation our safe harbor statement. I'll now turn it to Murdo Gordon to get us started.
Casey, thank you, and thanks everybody for being on the call this evening or this afternoon if you're on the West Coast of the U.S. It's our pleasure here at Amgen to host this discussion which will recapitulate some really exciting and important data that were presented, as Casey mentioned, here in Madrid at the 26th edition of the ESMO Medical Congress. So joining me this evening is our Head of Oncology Development, Jean-Charles Soria, our Senior Vice President of Oncology Global Development. Also joining me is Kaveh Niksefat, our Senior Vice President of Global Marketing and Access. And we're privileged to be joined by Dr. Charles Rudin, Director of the Memorial Sloan Kettering Cancer Center, who's one of the world's preeminent small-cell lung cancer physician researchers who joins us to lend us his perspective.
Dr. Rudin led the pivotal second-line phase III DeLLphi-304 study that established IMDELLTRA as a standard of care for relapsed small-cell lung cancer and is here today to provide his perspective on the first-line maintenance phase III study, the DeLLphi-305 results that were presented just a few hours ago here in Madrid. And of course, Casey will be here to answer questions as well who you are all familiar with. Today is one of those days where at Amgen we are able to live the company mission and our mission at Amgen is very simple, it's to serve patients. And as you know my experience, I've been to many congresses and many ESMO meetings over the last few decades, but this meeting has been a special one, an extremely special one.
Today was the kind of day that here at Amgen we all appreciate because it allows us to fulfill that company mission. It allows us to work on a devastating type of cancer, small-cell lung cancer, and transform survival expectations. Our BiTE platform has demonstrated transformative survival benefit in hematologic malignancies and now in solid tumors. IMDELLTRA clearly demonstrates durable survival benefit in small-cell lung cancer. IMDELLTRA is becoming the cornerstone therapy for extensive stage small-cell lung cancer regardless of the combination choice including PD-L1s. We have broad global development program that has the potential to further expand the impact that IMDELLTRA can have on patients. Our innovative oncology portfolio is well positioned as one of our core six key growth drivers. It is our pleasure to be able to delve into these data with a bit more detail.
Before we do that, just a reminder of the strength of Amgen's portfolio of first-in-class and best-in-class medicines with Repatha in cardiovascular disease, EVENITY in osteoporosis, TEZSPIRE in severe asthma and nasal polyps and soon eosinophilic esophagitis, Dupixent for rare autoimmune diseases, BLINCYTO in ALL, and IMDELLTRA in small-cell lung cancer. We are committed to delivering these first-in-class and best-in-class medicines. We have a broad innovative pipeline across these therapeutic areas, and these differentiated medicines are in leadership positions in populations with strong opportunities where we address significant unmet need. In oncology, of course, BLINCYTO and IMDELLTRA illustrate our ability to translate biology and deep biological insight into differentiated medicines.
Just as a reminder, as we reported our second quarter results, we have a very strong portfolio with these medicines delivering over 26% YoY in Q2 and comprises now 70% of our second quarter sales. We are definitely building strong commercial momentum with these growth drivers. We are enthusiastic about the outlook given the momentum for these products with patients that still continue to be underserved across these diseases. Without further ado, I do want to transition to Jean-Charles so that we can delve deeper into our program.
Thank you. Amgen Oncology R&D strategy is focused on delivering differentiated and transformative therapies for patients with hard-to-treat solid tumors and hematological malignancies. Our strategy is anchored in two core pillars, the T-cell engagers and precision therapies, which include small molecules directed at difficult-to-drug targets and antibody drug conjugates. Today, we will focus on the T-cell engager platform called BiTE. T-cell engagers are bispecific antibodies that physically connect a patient's T-cell directly to cancer cells, forcing an artificial synapse that allows the immune system to recognize and destroy the tumor. One arm of the T-cell engager, which is an antibody, latches onto a specific protein, which is a tumor-associated antigen on the cancer cell, while the other arm of this bispecific antibody binds to the CD3 receptor on the T-cell.
This close physical link activates the T-cell to release cytotoxic molecules that will kill the cancer cell or aim at least at killing the cancer cell. At Amgen, we are pioneers of BiTE medicines. The column on the left is where we started this story of bispecific T-cell engagers or BiTEs when the technology was new and the impact was uncertain. We have learned and built upon the innovation that brought us BLINCYTO, which was the first-ever T-cell engager approved, and we have expanded the impact of BiTE medicines into solid tumors. We have engineered second-generation BiTEs with convenient IV infusions and are exploring the potential for subcutaneous administration. We have navigated treatment concerns and have achieved mostly outpatient administration and reduced monitoring for our BiTE medicines, improving the overall patient experience. We have also improved the tolerability of our medicines through effective management strategies.
These were not trivial undertakings, and we have generated a high degree of institutional knowledge and expertise along the way for how to develop, manufacture, and commercialize BiTE medicines. This is clearly a strong platform for the company. The evolution of our BiTE platform is what brought us BLINCYTO, a CD19 targeting BiTE that has revolutionized survival in B-cell acute lymphoblastic leukemia. BLINCYTO was our first approved BiTE medicine and has dramatically changed the treatment on B-ALL. IMDELLTRA, a DLL3 targeting BiTE, has revolutionized survival in small-cell lung cancer. Xaluritamig is an investigational STEAP1 targeting BiTE that is rapidly advancing through phase III in prostate cancer. Xaluritamig, as you can see, is designed to bind STEAP1 on tumor cells and CD3 on T-cells, directing T-cell activity towards STEAP1-expressing prostate cancers.
Xaluritamig is being developed for all comers with no biomarker testing needed as the STEAP1 is highly expressed in prostate cancer. Xaluritamig development is significant and encompasses broad different stages of prostate cancer. With Xaluritamig, we are covering the waterfront of prostate cancer by pursuing a parallel development path across various prostate cancer disease stages, where there remain large patient populations with significant unmet need. The phase III MCRPC, Metastatic Castration-Resistant Prostate Cancer program, is testing two chemo-free regimens, Xaluritamig as monotherapy and Xaluritamig in combination with abiraterone in distinct late-stage treatment settings. We are also quickly moving to the earlier stage of prostate cancer, following the approach we pioneered first with BLINCYTO and now with IMDELLTRA. Our conviction in Xaluritamig's potential has led us also to this parallel investment approach.
We have introduced the BiTE strategy and platform, and now let's return to IMDELLTRA, a medicine that is transforming the standard for survival in small-cell lung cancer. Small-cell lung cancer is a devastating and rapidly progressing disease with survival often counted in months. There has been limited innovation in the field, and recent advancements have generated modest improvements in overall survival in the first-line setting. The question for us when designing the DeLLphi-305 study was whether adding IMDELLTRA to continued durvalumab treatment could improve outcomes in patients whose disease had not progressed after induction therapy. We gain initial insight into this approach from a phase I-B first-line maintenance study, DeLLphi-303. Some of you may recall that data from this study were presented last year and provided us insights into IMDELLTRA's ability to improve survival.
Today, we are pleased to share updated survival that are available in an e-poster and will be presented on Monday here at ESMO. With an additional year of data, we have now observed in the first-line maintenance setting a median overall survival of 37.9 months. This is remarkable data in this difficult-to-treat disease. It is now my pleasure to introduce Dr. Charles Rudin, a world expert physician scientist in small-cell lung cancer, to walk you through the transformative data from the DeLLphi-305 first-line maintenance phase III trial that was just presented a few hours ago during the presidential symposium here in Madrid at ESMO.
Well, thank you, Jean-Charles. It's a pleasure to be able to review these data, which I think are really quite spectacular. This data was presented by Jacob Sands in the meeting today. I was not part of the study directly, but I am quite familiar with the data and happy to go through it. The DeLLphi-305 trial was designed as a randomized phase III trial comparing a backbone, which is a current standard of care in the maintenance setting, that is IMFINZI, versus the combination of adding IMDELLTRA to IMFINZI. The trial was a one-to-one randomization, quite straightforward, with a primary endpoint of overall survival. Patients were randomized after completing four cycles of induction chemotherapy with immunotherapy, and patients had to at least have stable disease at that point to be eligible for enrollment. Key eligibility criteria are listed here.
I'll just point out that patients with brain metastases, both untreated and treated asymptomatic brain metastases, were allowed on study. The protocol was randomized and stratified for the presence or absence of brain and liver metastases, the response to first-line chemo IO, and the type of platinum used in that regimen. The secondary endpoints were progression-free survival and then subsequently overall survival. The trial was designed to first analyze OS, overall survival. If meeting that endpoint, progression-free survival was analyzed, and subsequently response rate and safety were considered. Next slide. This slide shows the baseline characteristics of patients enrolled in this trial, and you can see that in general, these are well-balanced arms. I'll point out that about 20% of the patients had brain metastases going into the study, and about a third of the patients had liver metastases on both arms. Next slide.
This is the data on the primary outcome of overall survival, and you can see a clear separation of the curves here. Hazard ratio of 0.42 with a P value of less than 0.001. The curve separated early, and that separation looks like it will be maintained. Essentially consistent in the shape of the curves with the phase I-B data that Jean-Charles showed earlier. Dramatic results and a clear improvement. Next slide. Subset analysis looking at pre-specified subgroups suggested benefit really across the board in all relevant subsets, including those patients with or without brain metastases, with or without liver metastases. So really a clear benefit across the board. Next slide. This slide shows the data for progression-free survival, which I think is also quite striking. In the maintenance setting on small-cell lung cancer patients, we tend to progress pretty quickly.
You can see on the IMFINZI curve, the control curve. In contrast, the combination really extends things out a median of 7.4 months versus 1.9 months in the control arm. Here, the hazard ratio is 0.34 with a P value of less than 0.001. Again, clear benefit. I would point a little bit to the tail of the curve. This is still early data with a median follow-up for progression-free survival on the order of 14 months. But clearly it looks like these curves are holding up. Next slide. Again, if we look at pre-specified subgroups, clear benefit across the board, brain metastases, liver metastases, et cetera. Next slide. In the maintenance setting, we rarely see response. These patients have had their major cytotoxic therapy as induction. Maintenance is really a time when patients are continuing on immunotherapy, and the goal there is really to avoid progression.
But here we can see that on the IMFINZI control arm, responses were seen in only 4% of patients. I think that is what we would sort of expect. In contrast, the addition of IMDELLTRA here leads to an overall response rate in the maintenance setting, which is kind of remarkable, 26%. On the right, the durability of that response is also, I think, striking, with over half of the patients who are responders still in response one year later. Quite an important result, I think, for patients. At the time of data cutoff, about 44% of the patients on the combination arm are still on drug. In contrast, only 11% of those on IMFINZI alone. Next slide. Safety is a clear concern here, and of course, adding two drugs, you do see more adverse events.
I would point out that those adverse events were quite manageable, really across the board. If we look at treatment-related adverse events that led to discontinuation or holding of the drugs, it is really a small minority, 3% for each of the two drugs. No fatal events on the combination arm attributable to drug. Next slide. Two of the key toxicities that we think about with the BiTE molecule, like IMDELLTRA, are cytokine release syndrome and ICANS. You can see here that those were observed on the combination arm, but really at strikingly low rates. Again, this was, to me, very striking data. Only a single patient on the combination had Grade 3 CRS, and none of the patients had Grade 3 or above ICANS. This is actually better safety data than what we have seen previously in patients who had recurrent disease treated with IMDELLTRA.
I think the reason for that, if I can speculate, is they were really treating minimal residual disease at this point as maintenance rather than progressive disease, which is often quite aggressive in patients with small-cell lung cancer when it recurs. The events that did occur were quite manageable, as noted here, with very low rates of use of drugs like tocilizumab. Next slide. In conclusion, this combination strikingly and significantly improves overall survival, progression-free survival, and leads to objective response in maintenance. In contrast to IMFINZI alone for patients with extensive stage small-cell lung cancer who have not had progression on first-line chemotherapy, 58% reduction in the risk of death, 66% reduction in the risk of disease progression or death, and an overall response rate in the maintenance setting of 26%.
The survival benefit really extends to all subgroups analyzed, including those patients with brain metastases, liver metastases, and irrespective of the chemotherapy combination used in induction. I think these are practice-changing data. This clearly defines a positive benefit-risk profile for patients with this otherwise very lethal disease. I will stop there. The study was published concurrently with the presentation today in The New England Journal of Medicine, and additional details can be found in that manuscript. We would of course like to thank the patients, the families, the investigators, and clinical site support. This was a big effort involving many people around the world and was supported by Amgen and AstraZeneca.
Thank you, Dr. Rudin, for a great presentation. Now let's look at our overall IMDELLTRA clinical development program. As you can see, we are pursuing a broad global clinical program with IMDELLTRA, establishing it as the cornerstone therapy in small-cell lung cancer. Our ongoing phase III studies are intended to move earlier in the treatment paradigm, and we are optimistic that these studies will demonstrate transformative first-line survival. In addition to the original registration-enabled study in second-line or later small-cell lung cancer and the data we have presented today, we are also investigating IMDELLTRA in two frontline settings. As first-line induction and maintenance with IMDELLTRA combined with chemo immunotherapy in the randomized phase III trial, DeLLphi-312. In the limited stage, we are studying IMDELLTRA following concurrent chemoradiotherapy in the randomized phase III trial, DeLLphi-306.
We are also pursuing flexible dosing to align IMDELLTRA with other treatment regimens and to further improve the patient experience. With extended IV dosing regimens have presented a well-known cancer in DeLLphi-309, and with subcutaneous dosing has been explored in DeLLphi-315. We are establishing IMDELLTRA as the cornerstone therapy in small-cell lung cancer. It is already a standard of care based on the phase III second-line data, DeLLphi-304, but we are also evaluating novel combinations of IMDELLTRA with the B7-H3 ADC, DeLLphi-310, and with DLL3 ADC, DeLLphi-313 with the DLL3 ADC. Additionally, we are exploring IMDELLTRA's impact beyond small-cell lung cancer. IMDELLTRA's profound data in small-cell lung cancer provides us confidence to explore IMDELLTRA in neuroendocrine carcinomas, as we seek to extend IMDELLTRA's impact into other DLL3-expressing malignancies.
We plan to evaluate IMDELLTRA both as a monotherapy and in combination in neuroendocrine malignancies beyond small-cell lung cancer and in other DLL3-expressing malignancies. There is clearly more to the IMDELLTRA story, but let's look at the progress we have made today in IMDELLTRA's currently approved indication. IMDELLTRA is an established standard of care in second-line or later extensive stage small-cell lung cancer. IMDELLTRA has revolutionized survival in second-line plus extensive stage small-cell lung cancer, extending the median overall survival by more than five months. IMDELLTRA is currently approved in over 15 markets globally with over 18,000 patients treated since launch. In the U.S., IMDELLTRA is available at more than 2,000 U.S. sites of care, with over 65% of sites that have used IMDELLTRA that are in the community setting. Recent reductions in monitoring time will hopefully allow us to reach additional patients in this approved indication.
Significant opportunity remains in the second-line setting, as chemotherapy continues to be a common treatment option. Moving IMDELLTRA earlier in the small-cell lung cancer continuum is important. In the currently approved indication, there are 40,000 eligible patients in the U.S. This will allow us to reach a significantly larger population and giving IMDELLTRA observed durability to also treat patients for longer periods of time. As you can see in this slide, IMDELLTRA has redefined survival for small-cell lung cancer. The evidence is clear and compelling, and we hope all of you are as excited about what this means for patients with small-cell lung cancer as we are today. Given the transformative benefit observed, we are working to rapidly file the phase III data we have shared today with regulatory authorities around the world.
In summary, IMDELLTRA is revolutionizing the treatment of small-cell lung cancer across multiple dimensions of care. We have observed unprecedented durable survival with additional phase III studies underway. We are working on reduced monitoring times and exploring alternative dosing regimens and subcutaneous delivery. We are rapidly advancing a broad global clinical development program to firmly establish IMDELLTRA as the cornerstone therapy for small-cell lung cancer. We really would like to take the time to thank all the patients, the investigators, and the staff that have made all of this possible. With that, I would turn it back to Murdo for Q&A.
Thank you, Jean-Charles. Thank you, Dr. Rudin. I'd like to thank one more group of people, Jean-Charles, and that's you and your development organization. Thank you for working so hard to deliver a profound data set and for conducting an exceptional clinical trial. Much appreciated. So with that, let's turn it over to Krista for our first question. Krista?
Thank you. If you would like to ask a question, please press star followed by the number one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one again. Again, to ask a question, press star one. Our first question comes from Salveen Richter with Goldman Sachs. Please go ahead.
Thank you for taking our question. Congratulations on the data, it is [inaudible] on for Salveen. Maybe if you could help frame the average duration of therapy under the expected first-line maintenance label compared to what you are currently seeing in the approved second-line setting. How does this level of efficacy here in DeLLphi-305 help to de-risk the ongoing phase III induction study? Do you think that this type of high bar may be specific to maintenance alone? Thank you.
Okay, Kaveh, why don't you start with the first question on duration of therapy, and then we will have Jean-Charles comment on is there a read-through from DeLLphi-305 to the ongoing maintenance stage trial.
Salveen, thanks for the question, and thanks for calling in on a Saturday. We appreciate it. To give some comparison from the trial setting, in DeLLphi-305, we saw that the median duration of treatment was 46 weeks. To put that in comparison, in DeLLphi-304, in the second line, we saw a median duration of therapy of 18 weeks. Now, obviously, in DeLLphi-305, we are still continuing to follow those patients. As you saw in DeLLphi-303, we saw an extended use from those patients going out all the way to 38 months. So we think there is going to be a meaningful step-up in overall duration of therapy as we move into the earlier lines and extend survival even longer than we were in the second line.
Jean-Charles?
Yes, thank you. Well, it is rare to have a medicine that hits two consecutive phase III trials, achieving all primaries and secondary endpoints in heavily pretreated patients and then in patients who are in the first-line setting who have been debulked by the induction chemo immunotherapy. So I do not know the future and would not predict it, but I feel very confident and sleep very well about what the induction maintenance phase III trial will bring to the patients.
Thank you, Jean-Charles. If you sleep well, I sleep well. Krista, the next question, please.
Your next question comes from the line of Evan Seigerman with BMO Capital Markets. Please proceed with your question.
Hi, all. Thank you so much for taking my question. Congrats on the data. Kind of a follow-up to the prior question. Clearly we know that there's a great impact of the drug in the maintenance study. But as you move towards the phase III induction that you've been talking about, how do you think about the importance of the cytotoxic chemotherapy kind of reducing tumor burden and then use of the BiTE to kind of continue the immune effect versus having it all done at once, kind of in a frontline first induction type therapy? Do you think that's kind of the effect changes as you move forward in treatment? Thank you.
Yes. I would say that, and thank you for the question. We started with the maintenance setting because it was very rational to bring tarlatamab after debulking the tumor because we knew we were very likely to have higher efficacy and better tolerability. It's exactly what we saw in a very profound manner and consistent across every single subgroup analyzed. In the induction and maintenance setting, we would like to reach all the patients. As you know, around 20% of the patients that start induction don't make it to maintenance. It can vary across trials, but it's in that range, 20%, 25%. So there is a desire to make sure every patient with metastatic small-cell lung cancer has access to the drug.
The reason to combine the three of them is that they are highly complementary and might act in ways that allow a broader number of cancer cells to be addressed. The chemotherapy is debulking. The PD-L1 is calling the immune system by making it visible and trying to recruit T-cells from the broad systemic nature of the immune system. But IMDELLTRA per se, is bringing T-cells into the tumor to directly fight against the cancer cells. So you are adding a way to tackle the disease by three complementary angles that make a lot of sense and might allow us to treat, therefore, the global number of patients with small-cell lung cancer.
Thank you, Jean-Charles. Krista, next question, please.
Thank you, Evan. Your next question comes from Matt Phipps with William Blair. Please proceed with your question.
Hi, this is Madeline on for Matt. Thanks for taking our question. In the presentation at the conference, the ability to treat beyond progression was discussed. Does Amgen plan to generate data to support that within IMDELLTRA? With that in mind, how could that impact the average duration of treatment in maintenance setting? Thank you.
Yeah, interesting question. Maybe I can ask Dr. Rudin to comment on treatment beyond progression.
Yeah, I think the trajectory of disease when patients are on IMDELLTRA seems a little bit different than what we're used to with patients with small-cell lung cancer. We are seeing evidence of what we call oligoprogression, meaning progression at a few sites, one, two sites.
Without global progression. We've begun treating those patients with things like stereotactic radiation to control sites of disease progression while continuing on the BiTE to allow the patient to continue to benefit from that. We have seen patients who continue to benefit for many, many cycles after local therapy. That's not something we have traditionally used in small cell, but I think the landscape seems to change. As Dr. Sands pointed out, we're seeing that more and more.
Yeah. Thank you, Dr. Rudin. I would just add that it's something that is routine in EGFR mutant non-small cell lung cancer that has teached us that when you have systemic control and just a site of progression, there is no reason to give that up. You treat locally and continue, and that has allowed EGFR mutant non-small cell lung cancer to be continued on treatment sometimes for extra years.
Thank you both. Krista, next question, please.
Thank you, Madeline. Your next question comes from Michael Yee with UBS. Please go ahead.
Great. Thank you. Two-part question for Dr. Rudin. Thinking about the all-important first-line induction study, which obviously would be great to have, as well as the positive maintenance study you now have, can you just comment about how we should think about the overall safety and AE profile of the triplet combination in first line, and thinking about that obviously as why the maintenance study you are reading out here today makes a whole lot of sense. I just wanted to think about the induction safety profile and maybe how relevant induction is if you already have a maintenance label. That is the first question. The second is, obviously, Dr. Rudin, you must be aware that there was also ADC PD-1 combo data for DLL3 that seemed quite attractive and safe and very high response rates.
Maybe you could just comment about that, because I do think Amgen is doing a combination with ADCs as well. I just wanted to think about how ADCs fit into the mix. Thank you.
Yeah, two great questions. First, the first-line induction. One of the basic fundamental rules of oncology is you give your best drug first. This is one of the best drugs, if not the best drug that we have for this disease, so we really want to push it into the first-line setting. As Jean-Charles said, we want all patients to be able to benefit from this. The safety data with the IO combination that was used in maintenance in this study really supports that we're not going to see additional toxicity. I think if we were going to see major tox signal, it would be because of the combination of two, if you will, inflammatory molecules. Of course, the proofs in the pudding will need to see that.
But the initial data that we've seen in the first-line setting has been reassuring in that context, and we'll see how that plays out. But I actually think the data we saw today helps to reinforce that this should be a safe combination. You're right, there's a lot of exciting data with the ADCs and ADCs in combination with PD-1s and PD-L1s in small-cell lung cancer and really across the board in oncology. I think that is an exciting area and something to build on. Some of the ADCs do seem to have a higher response rate in recurrent disease than any standard chemotherapy, and there's a lot of interest in pushing those into the first-line regimen, and I think IMDELLTRA can be an important backbone for those studies.
Yeah, I would just add to that we rejoice when innovation is made available to small-cell lung cancer patients. ADCs are a sophisticated and elegant way to deliver chemotherapy at the door of the cancer cell. They debulk. We have demonstrated that debulking with chemo followed by IMDELLTRA PD-L1 works. But we are also contemplating doing that with chemo induction. That absolutely can be done also, in our opinion, with ADCs, with IMDELLTRA anti-PD-L1. That will lead you to a regimen that is pretty novel, that we are excited and actively enrolling in our DLL3 ADC IMDELLTRA combo and the B7-H3 ADC IMDELLTRA combo, and a few more to go.
Exciting. Thank you, Jean-Charles. Thank you, Dr. Rudin. Krista, next question, please.
Thank you, Michael. Your next question comes from the line of Jeff Meacham with Citigroup. Please proceed with your question.
Hey, guys. Thanks so much for taking our question. This is Jarwei on for Jeff. Maybe just two questions for us. First of all, on the earlier question on IMDELLTRA's treatment duration, could there be any evidence, whether it be now or later on, that could support a finite course that preserves benefit while reducing burden and capacity requirements and cost? And then also maybe just thinking about commercial expansion, what lessons from the high number of treated patients and existing community footprint are most relevant as IMDELLTRA expands into first-line maintenance, and where do you still see the greatest access for capacity constraints? Thank you.
Jarwei, I apologize, but we're having a little trouble picking that question up, if you wouldn't mind just repeating for us because I think we're picking up static on the long-distance line here.
Oh, sure. How about now? Can you hear me clearly?
Yeah. Just maybe briefly first question and then briefly second question. I think we got some of it.
Okay, sure. Yeah, this first question basically, any evidence that could support a finite course of treatment while preserving benefit and reducing burden and capacity requirements and costs? Second question was more on lessons learned so far of IMDELLTRA treatment that could be helpful as you move IMDELLTRA into first-line maintenance, and where do you still see greatest access or capacity constraints?
Okay. Thank you for that question. When you have an unforgiving disease that comes with a diagnosis in January, when you can tell half of the patients that they won't be there at Christmas, it's hard to imagine withholding continuous treatment with these efficacies and well-tolerated for these type of patients.
Great. Kaveh, do you want to handle the market question?
Yeah, so look, in terms of market, whenever you have got a drug that delivers profound efficacy and improvement in the safety profile in an earlier line of therapy, you are really going to see an acceleration of behavior change across the market. We are incredibly excited about this data set in the front-line setting for small-cell lung cancer.
The best analog I have got from my experience here is two years ago at ASH when we released the COG AALL1731 data on pediatric ALL, and you saw a rapid adoption in the marketplace of that data. So taking the profound efficacy that we have already done, we are also seeing an ease of access coming from the reduced monitoring requirements. As you know, we started with 22- 24-hour monitoring. Recently in the U.S., we have gone down to six to eight-hour monitoring. In this study, we were down to one to two-hour monitoring.
That is going to enable additional sites to activate to be able to treat patients with this medicine in the front-line setting, but it is also going to increase the capacity at sites that are already activated being able to handle the increase in patient caseload overall. The combination of those factors should really add to the benefit. Of course, we are also adding to the profile with the extended dosing, as Jean-Charles referred to in DeLLphi-309, an ongoing investigation with subcu therapy which will continue to ease the accessibility of the medicine in the U.S. and across the world.
Great, thank you. Krista, next question, please.
Thank you, Jeff. Your next question comes from the line of Jay Olson with Oppenheimer. Please proceed with your question.
Oh, hey guys. Congrats on these impressive results and thanks for hosting this event. Any preliminary thoughts on resistance mechanisms to IMDELLTRA? Do you think IMDELLTRA-resistant or refractory patients could still respond to other DLL3-targeted therapies? Related to that, according to your analysis, are there any patient subgroups that may achieve better OS benefits with IMDELLTRA, and specifically, would DLL3-positive patients maybe have prolonged survival? Thank you.
Thanks for the question, Jay. I'll ask Dr. Rudin to address those two.
Yeah. We're still learning about resistance, and there's emerging data, I would say at this point it's anecdotal, multiple mechanisms of potential acquired resistance to this class of drugs. One would be downregulation of target, and that has been seen. Another is actually on the host side, an alteration in the T cells that are actually being stimulated. There's at least one case where a progressing lesion was biopsied, and it was shown to be mostly actually suppressor T cells as opposed to cytolytic T cells in that lesion. I think that actually tells us about the benefit of stereotactic radiation to a progressing lesion. The reason for resistance in oligoprogression may be more on the host side than actually the tumor. We're still learning about this. It's an active area of investigation is, I think, the best I can say.
What was the subgroup? Is there any subgroup that has one base?
The subgroup analysis that was done in this trial, and you have to find. There's really no subgroup that shows a lack of benefit. It's really across the board.
Thank you, Dr. Rudin. Krista, any additional questions?
Thank you, Jay. Your next question comes from the line of Terence Flynn with Morgan Stanley. Please proceed with your question.
Great. Thanks so much. Congrats on all the progress with IMDELLTRA. A two-part question. I guess you alluded to this, but maybe just any timeframe for moving into some of these other tumor types that you alluded to during your prepared remarks, and when we might see some data there beyond small-cell lung cancer. The other question is just obviously this has proven out the BiTE platform on the solid tumor side. Maybe just remind us the broader scope of your efforts here to keep moving forward with additional BiTEs and solid tumors. Thank you so much.
Thanks, Terence. I'll ask Jean-Charles to address those two questions.
Thank you. We have already reported activity of IMDELLTRA in prostate neuroendocrine carcinoma. We have an ongoing phase II trial with the French collaborative group in Europe actively recruiting in neuroendocrine carcinomas of the lung. We are planning other studies in neuroendocrine carcinomas of the GI, of the lung, but also in other DLL3-expressing tumor types. I think there is more than 50 published case reports, but I might ask Dr. Rudin, who certainly has treated non-DLL3 positive patients outside small-cell lung cancers, who might be coming, what has been his experience?
Yeah. DLL3 positive tumors tend to be the high-grade neuroendocrine tumors, and there are many of these. In the prostate world, this is certainly a mechanism of acquired resistance that we're seeing increasingly frequently now. We also see high-grade neuroendocrine tumors in the bladder and other sites. Other tumors that express DLL3 include melanoma, which would be another indication. Some of the gliomas, some brain tumors actually express a decent level of DLL3. A rare but important population is pediatric patients with neuroblastoma. This is a real unmet need, and we have seen good expression there and preclinical data really suggesting efficacy in targeting DLL3. So those are some of the diseases we could go after.
Thank you.
Great. Thank you both. Krista, perhaps our penultimate question here as we come up close to the half hour.
Certainly. Thank you, Terence. Your next question comes from the line of Gregory Renza with Truist Securities. Please proceed with your question.
Greg, good evening, Amgen team and doctors. Congratulations on the compelling data. Thanks for taking my question. As alluded to earlier, there are several DLL3 T-cell engagers that are coming online, including tri-specific, several global assets. I just wanted to comment from apart from being first and certainly having this very meaningful data today, what does make IMDELLTRA just structurally different? What do you highlight as the competitive differentiations more structurally when it comes to your asset versus the others that are coming? Thank you very much.
Thank you. DLL3 is an exquisite target. It is very unique in the sense that it is expressed at the surface of cancer cells and it is intracellular in normal cells. That gives you a very clean and unique target that is universally expressed in small-cell lung cancer and neuroendocrine tumors. Our T-cell engager has demonstrated indisputable activity across all endpoints analyzed in two consecutive phase III trials. We are very excited by that. It is not just being first, it is that the magnitude of the benefit that is observed is establishing these as the standard of care in second line and beyond, and now in first line maintenance. Other assets will need to benchmark against this DLL3 T-cell engager with survivors that have been significantly stable.
And potentially in multiple types of combinations and multiple settings.
Absolutely.
Thank you for the question. Maybe our last question, Krista, please.
Thank you, Gregory. Your next question comes from the line of Gary Nachman with Canaccord Genuity. Please proceed with your question.
Good afternoon, guys. This is Arsalan Kamran on for Gary Nachman, and congrats on the data. Thank you for taking my question. My questions are, how does management think about the balance between internal development and external BD in oncology specifically? Given the T-cell engager franchise, which modalities or mechanisms would it most likely to bring in, if at all? What stage of development would be the focus? Thank you.
Well, it's an exciting question to land on. Obviously, we have a very strong oncology team, both in discovery research and under Jean-Charles' leadership in clinical development. It's important when you have a world-class team like that they remain busy. We have a great internal pipeline of exciting assets, and we continue to be active looking at best-in-class or first-in-class potential medicines on the outside of Amgen. We continue to maintain a disciplined approach to capital allocation and business development. At this point in time, when you sit at a meeting like ESMO here in Madrid and you look at the substrate of innovation that is happening in small-cell and beyond, it's clear that this is a renaissance, if you will, in cancer drug discovery and research, and it's exciting.
Given the capabilities as Amgen, it's a really, really exciting place to be. As we look at the future, we're also looking at the present, and it's our job now to take these data that have been presented and shared here at the meeting. Among other data, Dr. Rudin also presented an extension, a follow-up on the DeLLphi-304 data. We have the DeLLphi-303 extension. The full suite of evidence behind tarlatamab really demonstrates that this is a cornerstone therapy, foundational to the treatment of small-cell lung cancer now. I think it's fair to say that the quality and consistency and magnitude of the treatment effect size here even exceeded our very ambitious aspirations for these trials. It's our job now to translate that into clinical change.
As such, we've mobilized our medical teams and made sure that NCCN guidelines committees have these data and aware of it, making sure that we file rapidly with the FDA, making sure that as we launch the second-line indication globally, we prepare for the addition of front-line maintenance. Seriously exciting times here. Most importantly, exciting to be able to bring hope to these patients with this very, very difficult diagnosis. With that, Krista, thank you for the Q&A session. Thank you all for attending. We'll close it out here, and we look forward to engaging with all of you over the next weeks and months. From Madrid, it's good night. That's not just.
Ladies and gentlemen, this does conclude our investor call from the European Society for Medical Oncology Congress 2026. You may now disconnect.