There will be a question-and-answer session. To ask a question during the session, you will need to press star one and one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one and one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Rafael Amado, President and Head of Global R&D. Please go ahead.
Hi, everyone. Thank you so much for joining us today. I'm Rafael Amado, Zai Lab's President and Head of Global R&D. Before we begin, we will be making forward-looking statements today, and I ask you to review slide two for further details. Moving to slide three, during today's call, we will be discussing the updated monotherapy phase I dose escalation and dose expansion clinical data of ZL1310, our investigational DLL3 targeted ADC. Dr. Patel, one of the lead researchers for this trial, is here to present the data, and we'll be presenting the poster at ASCO later this afternoon. Dr. Patel is a hematologist, medical oncologist, and serves as the Director of Drug Development for Florida Cancer Specialists and is an Associate Director of Drug Development for Sarah Cannon Research Institute. Following Dr. Patel's presentation, I'll discuss next steps for the program and then open the line for questions and answers.
Dr. Patel is unable to stay for the Q&A portion, but we are pleased to be joined by Dr. Smiley, who is the Director of Clinical Research and CEO at Next Virginia, Co-Director at the Virginia Cancer Specialists Research Institute, and a Clinical Assistant Professor at Johns Hopkins. I will now pass it to Dr. Patel.
Thank you, Rafael. My name is Dr. Manish Patel. I'm the Director of Drug Development at the Florida Cancer Specialists and Sarah Cannon Research Institute. On behalf of my co-investigators, I'm excited to share the latest findings and insights from our ongoing phase Ia, 1b multicenter study evaluating ZL1310 in patients with recurrent small cell lung cancer. Later on this afternoon, we'll be presenting our poster at the 2025 ASCO meeting in the session entitled Developmental Therapeutics, Molecularly Targeted Agents in Tumor Biology, poster number 356. Small cell lung cancer accounts for approximately 15% of all lung cancers, affecting around 372,000 patients worldwide and resulting in approximately 270,000 deaths annually. It is characterized by a high proliferation index and early metastases, with up to 70% of patients developing brain involvement.
The prognosis remains poor, with a median overall survival of around 13 months, and there is an urgent need for novel treatment modalities and targets. Recently, DLL3 has become a validated target for small cell lung cancer and other high-grade neuroendocrine tumors. ZL1310 is a DLL3 targeted antibody-drug conjugate consisting of a humanized anti-DLL3 IgG1 antibody with a topoisomerase I inhibitor payload, with a cleavable linker that demonstrated promising clinical activity in patients with relapsed refractory extensive-stage small cell lung cancer, as previously reported. In particular, Zocilurtatug Pelitecan, we'll call it Zosie going forward, has some unique characteristics that may portend potential best-in-class treatment for recurrent small cell lung cancer. Namely, the high antibody affinity, relatively prolonged half-life, and clean and frequent DLL3 expression in tumors allow for targeted killing.
In addition, the cleavable linker and high DAR of eight allows it to have a strong bystander effect, leading to good clinical activity across a wide range of DLL3 expression, as you will see. On to slide number six. This is a study designed for our phase I trial, designed to evaluate the safety and efficacy of ZL1310 monotherapy in patients with recurrent extensive-stage small cell lung cancer following at least one prior platinum-containing regimen. Patients with asymptomatic brain metastases, both treated and untreated, were allowed, as well as patients who failed prior DLL3 targeted agents. The trial has evaluated six monotherapy dose cohorts with additional patients treated in expansion cohorts of 1.2, 1.6, and 2.0 milligram per kg of 1310 to optimize dose selection for pivotal studies. We highlight the 1.6 milligram per kg dose to draw attention to those results in multiple slides going forward.
In this update, 89 patients have been enrolled across six dose cohorts. Of these, 47% received one prior line of therapy, and 53% of patients have failed at least two prior lines of therapy. Notably, the 1.6, 2.0, and 2.4 milligrams per kg arms included 23%, 24%, and 29% of patients, respectively, and these patients all had three or more prior lines of therapy. 90% of patients received prior anti-PD-L1 therapy, 11% received prior DLL3 targeting therapy, and 30% of these patients had brain metastases documented as either target or non-target lesions, eight of which were untreated at the time of study entry. 74% of patients are available for efficacy assessment across doses and lines of therapy. Turning to safety on slide eight, the safety analysis set includes 89 patients who have received at least one dose of Zosie . In general, Zosie demonstrates a remarkably well-tolerated and manageable safety profile.
We are presenting the safety data in two cohorts: those receiving less than 2.0 milligrams per kg, that is 0.8 to 1.6 milligrams per kg, or those receiving 2.0 milligrams per kg or higher, to highlight the remarkable safety profile. Of note, only 16% of patients in the low-dose group required dose interruptions for any cause, and only two patients required dose reductions, and no patients discontinued treatment due to adverse events. The dose reductions were due to low-grade pneumonitis, fatigue, hyponatremia, and neutropenia. The data are even more impressive when we look at grade three or greater adverse events, with only 6% experiencing this level of toxicity. Overall, however, there were five patients who discontinued treatment, all at the higher doses, and one patient who died due to interstitial lung disease. This patient had previously received a high dose of chest radiation therapy.
While initially responding to therapy, the patient withdrew from the study and opted to forgo further care. On slide nine is a table of treatment-related adverse events that occurred in greater than or equal to 10% of patients. The most common treatment-related adverse events of all grade included anemia at 40%, neutropenia at 30%, nausea at 26%, and leukopenia at 23%. Grade three or greater heme toxicity was less than 5% in the lower dose group and only 26% in the higher dose group, indicating low systemic exposure of the topo-1 payload and plasma. Overall, there were nine patients who developed pneumonitis or interstitial lung disease. The low-dose group had two grade one ILD cases, and both of these recovered and were able to restart 1310 therapy. Now we turn to efficacy, beginning with the dose escalation results on slide number 10.
In October of 2024, we presented initial results of the triple meeting in Barcelona for 25 patients enrolled in the dose escalation, of which 19 were efficacy evaluable. At ASCO, we presented efficacy data on 28 patients enrolled in the dose escalation. These patients demonstrate a confirmed ORR of 68% and a disease control rate of 93%, with strong efficacy across all dose levels. Of the 19 responders, 10 remained in response between 2.8 and 9.1 months. Half of these are still in response, now greater than six months out. Turning to slide number 11, we are presenting efficacy by lines of therapy across dose escalation and expansion. Of the 89 patients treated as of April 1st, 74 patients have had at least one post-baseline tumor assessment.
The ORR remains quite robust at 67% in second-line patients with a disease control rate of 97% and decreases, not unexpectedly, in later lines. Twenty-nine of the 38 responders remain on study, with the longest surpassing nine months on treatment. The median follow-up of this group is 3.4 months, and the median duration of response cannot be estimated. Interestingly, 87% of patients with stable disease also remain on study, highlighting the potential durable benefit in these patients. On slide number 12 is the efficacy by dose level in patients treated with 1310 in a second-line setting. Across all dose levels in the second-line setting, unconfirmed ORR was 67%. Even more impressive were the results from the 1.6 mg per kg arm, where patients achieved an unconfirmed ORR of 79% and a disease control rate of 100%.
Together with a favorable safety profile, these data would support 1.6 mg per kg as a reasonable phase III dose, pending the completion of dose optimization, longer follow-up, and discussions with the FDA. The waterfall plot on slide 13 includes the 74 efficacy evaluable patients treated across all dose levels, demonstrating 89% of patients experienced a reduction in their tumor burden. Interestingly, 55% of patients with stable disease and tumor reduction continue on study. Indeed, the vast majority of patients had tumor reductions and remain on study, some with stable disease and deep decreases in tumor dimensions. Hence, the mature ORR may change over time. This next slide with a spider plot shows that most people achieved a response by their first tumor assessment, including one CR.
This is unlike other mechanisms of action and results in rapid onset of activity in patients with bulky disease and in those with brain metastases, with a median time to response of 5.6 weeks. In addition, frank progression is rare, and some patients continue on study past 11 months. In second-line patients treated with Zosie, patients achieve response by their first tumor assessment, typically plateau. However, there are a few who continue to deepen in their response. The longest ongoing patient is approaching 48 weeks, and the longest responder at the 1.6 mg per kg dose is over 36 weeks on trial. Turning to slide number 16, an interesting slide, brain metastases are very common in patients with recurrent small cell lung cancer, with up to 70% of patients experiencing such. Thus, activity in patients with brain metastases is an important factor for the treatment of these patients.
In our study, we had 22 patients, or 30% of patients, who had either a target or non-target lesion in the brain at study entry. The ORR of this cohort was 68%. However, the response in patients without prior cranial radiation was 86%. While intracranial disease response, regardless of target lesion, is ongoing through scan reviews, at least four patients with measurable target lesions and either no cranial radiation or cranial radiation longer than six months prior to study entry experienced intracranial tumor shrinkage of up to 70%. While we continue to evaluate intracranial activity in all the patients, we are highly encouraged by the data we observe. In conclusion, ZL1310 demonstrated an acceptable safety profile with low rates of drug withdrawal and low rates of high-grade adverse events.
It presented clear evidence of high anti-tumor activity in patients with relapsed or recurrent extensive stage small cell lung cancer, including those with brain metastases. Responses were particularly notable among patients who had undergone one line or prior platinum-based systemic therapy at the 1.6 mg per kg dose, and the stable disease rate may result in an increase in deepening of the responses as the follow-up is immature. Based on these findings, a phase III pivotal trial assessing ZL1310 in extensive stage small cell lung cancer patients is planned to start later this year. Thank you for your attention. We look forward to your questions and further discussions.
Thank you, Dr. Patel. Moving to slide 19, the safety and efficacy profile of ZL1310 continues to be compelling, with a great opportunity to significantly improve outcomes of patients with small cell lung cancer.
While the dose optimization study is still ongoing, the 1.6 mg per kg dose shows the most promising combination of response and tolerability thus far. With an unconfirmed response rate in second-line small cell lung cancer of 79%, a well-tolerated safety profile, and efficacy in brain metastases, ZL1310 has significant potential in this setting. While it is premature to assess the durability of response as the median follow-up in all patients is only 3.4 months, we note the longest ongoing response is 9.1 months, with 29 of 38 responders still on treatment. Based on these results, we will be initiating a registration study in second-line small cell lung cancer later this year. The study will be a randomized two-arm study comparing ZL1310 at the selected dose against investigators' choice of therapy. The trial is designed with overall survival as the primary endpoint.
For accelerated approval, we'll also assess confirmed overall response rate. Secondary endpoints include duration of response, progression-free survival, time to response, safety, and quality of life. Eligible patients will be those with extensive stage small cell lung cancer who have progressed after first-line platinum-based therapy and received only one prior line of systemic therapy. Key certification factors include the presence of brain metastases, chemotherapy-free interval, and choice of chemotherapy in the control arm. We expect to initiate this registrational study in the second half of this year, with a planned interim readout next year, which could potentially set the stage for an accelerated approval in 2027. Beyond second-line small cell lung cancer, we will also be pursuing opportunities in first-line small cell lung cancer and neuroendocrine carcinomas. Slide 20 summarizes the clinical development strategy and key catalysts in the next 12 months in these areas.
Given its favorable safety profile, ZL1310 is particularly well-suited for use in the first-line setting, either to enhance maintenance treatment or as a potential replacement for chemotherapy. These strategies are designed not only to improve outcomes, but also to reduce treatment burden for patients with extensive-stage small cell lung cancer. We've begun enrollment in the combo dose escalation portion of the study, which will be followed by dose optimization and then a pivotal combination trial after a defined follow-up period. We're also expanding the reach of ZL1310 into other DLL3-expressing solid tumors, particularly poorly differentiating neuroendocrine carcinomas. The estimated global prevalence of DLL3-expressing in NEC is roughly 350,000 to 400,000 patients. These are aggressive tumors with poor long-term survival outcomes and very limited treatment options. We're aiming to accelerate a phase I to potentially registrational study this year.
Together, these programs provide us with an opportunity to expand the reach of ZL1310 across multiple high-need tumor types, with the first regulatory submission targeted as early as next year. In conclusion, we're pleased with the promising data thus far for our DLL3-ADC program. Taking together the profile we've seen with ZL1310, high response rates, early and durable activity, and CNS activity, supports its competitiveness in the second-line setting. Importantly, we're achieving this efficacy with a highly manageable safety profile. Beyond these results, we're advancing into a randomized pivotal trial in second-line small cell lung cancer in the second half of this year, using the 1.6 mg per kg dose pending FDA agreement. I look forward to providing further updates on our DLL3-ADC program in the second half of this year. Now, operator, please open the line for questions and answers.
Thank you. Once again, as a reminder, to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Please stand by while we compile the Q&A queue. Our first question comes from the line of Yigal Nochomovitz from Citig roup. Please go ahead. Your line is open.
Hey, Rafael and team. Congrats on the data. I was just curious with respect to the therapeutic window, if you could comment on what you saw, perhaps at some of the higher doses in terms of efficacy and how confident you are that 1.6 is the right dose to take forward into the pivotal studies. Thank you.
Yes, thanks for the question. We started based on the therapeutic window that we had seen comparing two MPK with 1.6. And as Dr. Patel said, there was more ILD at two and above, although only two of them of the seven that were observed at two and above were grade three plus. With 1.6 and below, particularly with 1.6, we only saw two grade one that were able to be retreated. There is, as you saw in the dose response, a slight attrition as you go up with the dose. That is particularly due to the fact that, one, there's a plateau in the response curve, but also some of the patients need to be discontinued or interrupted. If you look at also a hematology toxicity, there's a difference where we only saw a 6% grade three plus with 1.6. You're right, the therapeutic window may still be narrow, but we have what we think is a good dose at 1.6.
We've been asked to study a lower dose, which is not unusual. FDA oftentimes does that. We are putting patients in 1.2 as well. We will very carefully look at these patients and make sure that they're measuring up both efficacy and safety-wise with 1.6. As we announced, we got fast track. We will also apply for VTD and hope to have a pretty fluid dialogue with FDA to be able to land on that dose. I mean, so far, it appears, based on the totality of the data, that particularly in second line, 1.6 is highly active with actually a very mild safety profile, particularly when compared with other ADCs and other classes. That's what I can say as to where we are now.
We will complete the randomization expansion and then present the entire package with some durability to FDA and make the decision. We hope to do that before we start the phase III.
Thank you very much, Rafael.
Thank you. We'll now move on to our next question. Our next question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead. Your line is open.
Hi, this is Albert Agustinos, dialing in for Jonathan Chang. Thank you for taking my questions. My question is, what is the dosing strategy and safety consideration for the combination trial given what we know from the monotherapy profile to date?
Yes. As you know, there's been already precedence of ADC supplanting chemotherapy in other diseases. Some of the very effective ADCs out there are moving into front line as well with chemotherapy-sparing regimens.
We wanted to be methodical in terms of combinations. Cisplatin and Etoposide is active, and it's active fast. In order to be able to discontinue chemotherapy and just use checkpoint inhibitors plus 1310, we have to demonstrate, A, combinability, but also that the activity is competitive and superior to the standard chemotherapy regimen that's available now. We are confident that that will be the case because in second line, we are seeing numbers that compare very favorably with chemotherapy upfront. What I can tell you is that we are finishing the Atezolizumab combination and have started the carboplatin combination along with Atezolizumab in front line patients. We will expand that as well.
As the field evolves because of the entrance of new agents like T-cell engagers, we will explore as well the possibility of combinations with T-cell engagers if those end up being part of the front line regimen. Our initial going in is that probably the front line combination will include Carboplatin, Atezo, and 1310. That is where we are now. We will continue the dose escalation and collecting efficacy data and safety data. So far, the safety has been unremarkable, and the efficacy has been quite good. We will make a decision after we collect all that data. Meanwhile, we are really focused on the second line.
Got it. Thank you.
Thank you. We will now move on to our next question. Our next question comes from the line of Anupam Rama from J.P. Morgan. Please go ahead. Your line is open. Hi, guys.
This is Priyanka On for Anupam. Can you quickly put the durability of ZL1310 into context of the competitive landscape of the refractory SCLC?
The follow-up, as Dr. Patel mentioned, is not very long. That is why we isolated the dose escalation because that is the one that has the longest. And just to reiterate what you heard, the median follow-up for that group of 28 patients was 6.9 months. The response rate was 68%. That is mature response rate. Everybody is confirmed. The disease control rate is 93%. This is across lines of therapies. We have still 10 patients remaining in response, just above 50%, 53%. Half of those responses are at six months or above. With that median and the number of patients still in response, that can give you a sense of what that durability may be, at least in that group.
You know the durability of other agents in this class, whether it's 5.7 or lower response rate, but durability more in the nine months with TCEs. For us, I think durability is around six or above would be considered clinically meaningful. For the rest of the patients, of the entire 74 patients for whom we have efficacy, the follow-up is 3.4 months, and the median has not been reached. If you look at the waterfall plot, you can see that many of these patients, close to 30%, are still early in the study. Their response and durability will continue because many of them are still continuing to be treated. We can, unfortunately, not give you a number now. We just have to wait. Obviously, the longer, the better.
Thank you. We'll now move on to our next question.
Next question comes from the line of Michael Yee from Jefferies. Please go ahead. Your line is open.
Hey, guys. Thanks. Good morning. Maybe just two questions also for the doctor. How are you thinking about using this potential drug, if approved, in second line as it relates to the competitor, Tarlatamab, which has survival data here? Although I think this morning here at ASCO, and I think published in the New England Journal, the durability came down. Maybe you could compare and contrast those two, and particularly the opportunity in first line for both of these agents, given Tarla versus this ADC. Thank you.
It's Alex Spiro. I just pulled up the New England Journal article this morning. Tarla is a great drug. You can't belittle it at all. The challenge is in the administration. The clinical trial obviously was a very selected site.
What that basically tells us, and the utilization is much lower just because it's really hard to get. Most physicians outside intense trial sites and the big academic centers can't really do it that well. I mean, obviously, I'm a researcher. I do a lot of things. Even our hospital can't do it and can't administer it just because of logistical implications, hospital reimbursement, etc., plus all the toxicity. It's obviously a good drug. I think for the general small cell community, which real world, of course, is sicker, older than a lot of these patients on study, I think an easy-to-administer outpatient drug will likely be given.
Even as Tarlatamab gets to be administered as an outpatient, and certainly Amgen is finally studying it, it's less significant cytokine release syndrome and eye cancer events that happen at all hours of the night, making it challenging to give in an outpatient scenario. I think it will largely be used because of ease of administration going forward. Certainly, you didn't ask the question. In other patients right now, comparing versus Topotecan and others, there's not even a question. Topotecan is just another drug we like to give.
Thanks, Dr. Spiro. I would just simply add that there are different mechanisms of action. Even though it's still anecdotal, we've, I think, treated up to four patients post-Tarlatamab. We've seen a complete response, a partial response, and some decrease in tumor diameters in a couple of other patients.
There will be combinations between ADCs and this modality, I think, as people start sort of working out how to treat this disease. There are clear differences in toxicity, although it's a highly active drug, as you saw.
Thank you. We'll now move on to our next question. Our next question comes from the line of Louise Chen from Scotiabank. Please go ahead. Your line is open.
Hi. Congratulations on the data. Thanks for taking my questions here. I wanted to ask you, what gives you confidence in a potential accelerated approval for ZL1310? What do you think the FDA needs to see for accelerated approval?
Yes. We've been having discussions with FDA about this potential. They have been unambiguous about the fact that accelerated approval is an option in the context of the randomized trial that we described earlier.
That would be based on comparisons of response rate. I think the agency and us are discussing what the numbers should be between both the control and the test arm. They obviously do want every patient to be approved by the time the analysis is done. They do not just want the number of patients. They want them followed for a period of time, probably around eight months or so. That number of patients would probably be around 100 per arm. We think that we could have that data in 2027 on file. We don't expect the agency to change its mind. Obviously, there will be an approved drug with full approval. I think they really realize that we need more drugs in this disease, that this is a different mechanism of action, different ease of administration.
We have received no signal that accelerated approval is a viable option for the drug.
Thanks. Can I have just one quick follow-up question? What do you hope to see in your combo data later this year? Any positive read-through from the data today to that data coming up?
I think it is early day for the combo data. I mean, all the patients are responding, and their responses are high. What we expect is that we will see upwards of 75% or so response. We obviously have to have a sufficient number of patients and sufficient durability to make sure that that study will be positive. We also will have to do some dose optimization, although the companion drugs and the doses are fixed. We do not think that we will have to do as many doses as we did with monotherapy in second line.
It will go a little faster. Time to progression will be important. I think we've learned today that it's in the fourth or so for Tarlatamab. We will be waiting for a period of time of seven months or so to see what percent of patients are still in response. It will take some time. We hope to be able to show some data towards the end of the year. We will wait until we have a clinically meaningful dataset that's informative.
Thank you.
Thank you. We'll now move on to our next question. Our next question comes from the line of Li Watsek from Cantor Fitzgerald. Please go ahead. Your line is open.
Hey, guys. Thanks for taking our questions. I wonder if you can just talk about the remaining items that you still have to align with FDA before you initiate a pivotal study. Is it just the going-forward dose? I'm just curious, is there a dose de-escalation protocol for the phase III trial? Can you clarify if you expect to enroll patients maybe pretreated with Tarlatamab into the trial just given you require only one prior line of therapy? Thank you.
Yeah. All very good questions. Some of them, we still need to agree with FDA. It's a second-line study. These patients will be Tarlatamab naive. In the control arm, the question is whether Tarlatamab will be required. The FDA has not asked us to include it. There are other studies out there for ADCs where they only include a single chemotherapy. We plan to include dealer's choice with three chemotherapies.
There will be dose modification guidelines for patients that have toxicities that call for resumption of the drug at a lower dose level. We hope that that won't be very high because we have seen that in very few patients at 1.6 if that ends up being the final dose. I think the most important thing is to land on the dose. We plan to update FDA on where we are with the totality of the data soon. We're putting that together. Then understand from them what else, if anything, is required for us to choose the dose. If they ask us to increase the number of patients or any other variation, we will complete that. Accrual has not been an issue for us. We think that we'll be able to have those data available before the initiation of the study.
Of course, the sooner we can do it, the better. That is really the main issue with regards to what's left with FDA in terms of agreeing on the study design. The issue of Tarlatamab, that hadn't come up, I'm sure it will come up in the next discussion. Tarlatamab is unfortunately not approved in many countries. Patients in the United States may see Tarlatamab. Overall, the use of Tarlatamab, if we start the study soon in the control arm, we don't expect it to be overly high.
Okay. Thank you.
Thank you. We'll now move on to our next question. Our next question comes from the line of Linhai Zhao from Goldman Sachs. Please go ahead. Your line is open.
Hi. Thanks for taking my question. Congratulations. Sounds great data. I have two questions.
The first question is about, can you elaborate more on the ILD occurrences, particularly on the two grade three and above ILD cases? What are those levels for those two cases? Also, did you do any more detailed data in terms of helping to understand the differences in the safety profile for the high dose versus the low dose? For example, maybe the analysis on the free payload concentrations, the correlation of the AE currents versus the duration of treatment. Any color to help us understand the differences here? Thanks.
Yeah. Good question. I'll focus on those two grade three and above. One was a grade three patient. The second ended up being a grade five patient. I think as Dr. Patel mentioned in his remarks, the patient was initially treated and then withdrew treatment.
The thing about ILD is that it requires some time for it to manifest. We had treated a number of patients at doses at two and above. We saw these two events at two, and the other one was at 2.4, relatively sort of concomitantly on time. That is what led us to institute guidelines for follow-up for these patients. The more you look for this, the more you see it, obviously. We review the scans for fibrosis very thoroughly prior to patients entering. We have learned that patients that had high doses of radiation, for instance, above 35 gray or 40 gray, are at higher risk. Obviously, dose is a factor. Be very vigilant with questioning the patients and performing PET scans. If we see grade one, then stop immediately and then resume when the patient recovers.
ADCs, there are all of them associated with ILD. I think we just have to be vigilant about this. I would just sort of echo that it's been seen as well with B7H3s. Also, our study was multi-center and multi-country. When you have multiple centers and patients with multiple lines of therapies, etc., you may see this more often. In general, we do not think that high-grade ILD is any different than anything that has been seen with other ADCs. I do not know, Dr. Spiro, if you want to comment about your experience with ILD and ADCs in this field.
Yeah. I mean, you said it very well. Bottom line is it happens with all ADCs, especially in lung cancer patients.
Anybody may have changed, but obviously, lung cancer patients that have been treated before with radiation, just COPD, or just having cancer in the lung, obviously, the levels seen here, in my mind, are not unexpected because we do see it in all. It does take investigators and physicians' diligence to monitor closely for signs and symptoms. In the studies, we're all used to it, and clinicians are used to it as well. If you look at other drugs that have been approved in the lung cancer space, their ADC, TDXD, as being the major example, it is certainly seen there as well at a similar frequency and a minimum.
Yeah. As I said before, it doesn't manifest right away. It generally takes about 60 days or so. A number of patients at 1.6 have passed that threshold. We're not seeing very many.
We just see a couple of them with grade one. We think that, as I said before, dose matters and that that dose should be associated with a low dose, a low rate, rather, of interstitial lung disease.
Thank you.
Got it. Thank you.
There are no further questions at this time. I will hand the call back to Rafael.
Thank you, Operator. Thanks to everybody that were on the call today. We will be presenting the poster later on today. Again, thank you for your attention. Operator, you may disconnect.
Thank you. This concludes today's conference call. Thank you for participating. You may all now disconnect.