Zai Lab at ASCO 2025: Promising Lung Cancer Drug Update

On Monday, 02 June 2025, Zai Lab (NASDAQ:ZLAB) presented at the American Society of Clinical Oncology Annual Meeting 2025, sharing promising updates on their drug ZL1310 for small cell lung cancer. The presentation highlighted both encouraging efficacy data and manageable safety concerns, outlining strategic steps for future trials and regulatory discussions.

Key Takeaways

• ZL1310 showed a 67% overall response rate in second-line small cell lung cancer patients.
• The company plans to initiate a Phase 3 trial in the second half of the year.
• Zai Lab is exploring first-line treatment opportunities and expanding into neuroendocrine carcinomas.
• Management is in discussions with the FDA for potential accelerated approval.
• Safety profile of ZL1310 allows outpatient administration.

Operational Updates

• Clinical Trial Progress: Zai Lab is preparing to start a pivotal Phase 3 trial for ZL1310 in second-line small cell lung cancer, targeting a 1.6 mg/kg dose.
• Combination Therapy: The company is concluding trials with atezolizumab and has initiated combination studies with carboplatin and atezolizumab, showing promising efficacy.
• Expansion into NECs: Plans to accelerate a Phase 1/2 study in neuroendocrine carcinomas this year, with regulatory submission aimed for next year.

Future Outlook

• Registrational Study: A study in second-line small cell lung cancer is planned for later this year, focusing on overall survival as the primary endpoint.
• Interim Readout: Expected next year, potentially paving the way for accelerated approval in 2027.
• First-Line SCLC and NECs: Zai Lab is pursuing opportunities in first-line treatments, aiming to replace chemotherapy.
• FDA Discussions: Ongoing talks focus on dose selection and study design to optimize ZL1310’s path to approval.

Q&A Highlights

• Dose Selection: Confidence in the 1.6 mg/kg dose is supported by a favorable therapeutic window.
• Durability: Early data shows promising response durability, with 53% of responders maintaining response.
• Combination Strategy: Future frontline combinations may include carboplatin, atezolizumab, and ZL1310.
• Competitive Landscape: ZL1310’s safety profile is advantageous for outpatient use and offers a unique mechanism of action.
• Accelerated Approval: The FDA considers accelerated approval viable based on response rate comparisons.

For a detailed understanding of Zai Lab’s strategic plans and clinical data, please refer to the full transcript below.

Full transcript - American Society of Clinical Oncology Annual Meeting 2025:

Operator: There will be a question and answer session. To ask a question during the session, you will need to press 11 on your telephone. You will then hear an automated message advising your hand is raised. Please be advised that today’s recording 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 and D.

Please go ahead.

Rafael Amado, President and Head of Global R and D, Zai Lab: Hi, everyone. Thank you so much for joining us today. I’m Rafael Amado, Zai Lab’s President and Head of Global R and 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 one dose escalation and dose expansion clinical data of ZL1310, our investigational DLL3 targeted ADC.

Doctor. Patel, one of the lead researchers for this trial, is here to present the data and will be presenting the poster at ASCO later this afternoon. Doctor. 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 Doctor Patel’s presentation, I’ll discuss next steps for the program, and then open the line for question and answers.

Doctor. Patel is unable to stay for the Q and A portion, but we are pleased to be joined by Doctor. Spara, who is the Director of Clinical Research and CEO at Next Virginia, co director at the Virginia Cancer Specialist Research Institute, and a clinical assistant professor at John Hopkins. I will now pass it to doctor Patel.

Manish Patel, Director of Drug Development, Florida Cancer Specialists at Sarah Kenner Research Institute: Well, thank you, Rafael. My name is doctor Manish Patel. I’m the director of drug development at the Florida Cancer Specialists at Sarah Kenner Research Institute. And on behalf of my coinvestigators, I’m excited to share the latest findings and insights from our ongoing phase one a, one b multicenter study evaluating ZL one three one zero in patients with recurrent small cell lung cancer. Later on this afternoon, we’ll be presenting our poster at the twenty twenty five ASCO meeting in the session entitled developmental therapeutics, molecular targeted agents, and tumor biology, poster number three five six.

So small cell lung cancer accounts for approximately fifteen percent of all lung cancers affecting around three hundred and seventy two thousand patients worldwide and resulting in approximately two hundred and seventy deaths annually. It is characterized by a high proliferation index and early metastases with up to seventy percent of patients develop developing brain involvement. The prognosis remains poor with a median overall survival around thirteen months, and there’s 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 one inhibitor payload with a cleavable linker that demonstrated promising clinical activity in patients with relapsedrefractory extensive stage small cell lung cancer as previously reported.

In particular, zosiluratug pelatikan, we’ll call it Zosi 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 d o three 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 DLO3 expression, as you will see. On to slide number six, this is a study design for our phase one trial designed to evaluate the safety and efficacy of Zosi, monotherapy in patients with recurrent extensive 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 d l three targeted agents. The trial has evaluated six monotherapy dose cohorts with additional patients treated in expansion cohorts of one point two, one point six, and two point zero milligrams per kilo of one three one zero to optimize dose selection for pivotal studies.

We highlight the one point six milligram per kilo dose to draw attention to those results at in in multiple slides going forward. In this update, eighty nine patients have been enrolled across six dose cohorts. Of these, forty seven percent received one prior line of therapy, and fifty three percent of patients have failed at least two prior lines of therapy. Notably, the one point six, two point zero, and two point four milligrams per kilo arms included twenty three percent, twenty four percent, and twenty nine percent of patients respectively, and these patients all had three or more prior lines of therapy. Ninety percent of patients received prior anti PD L1 therapy, eleven percent received prior DLL3 targeting therapy, and thirty percent 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.

Seventy four percent of patients are available for efficacy assessment across doses and lines of therapy. Turning to safety on slide eight. The safety analysis that includes eighty nine patients who have received at least one dose of Zosi. In general, Zosi demonstrates a remarkably well tolerated manageable safety profile. We’re presenting the safety data in two cohorts, those receiving less than two point zero milligram per kilo, that is zero point eight to one point six milligram per kilo, or those receiving two point zero milligram per kilo or higher to highlight the remarkable safety profile.

Of note, only sixteen percent 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 six percent experiencing this level of toxicity. Overall, however, there were five patients who discontinued treatment, all at the higher doses, and one patient who died during 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 forego further care. On slide nine is a table of treatment related adverse events that occurred in greater than or equal to ten percent of patients. The most common treatment related adverse events of all grade included anemia at forty percent, neutropenia at thirty percent, nausea at twenty six percent, and leukopenia at twenty three percent. Grade three or greater hemotoxicity was less than five percent in a lower dose group and only twenty six percent in the higher dose group, indicating low systemic exposure of a topo one payload in plasma. Overall, there were nine patients who developed pneumonitis or interstitial lung disease.

The low dose group had two RAID one ILD cases, and both of these recovered and restart were able to restart one three one zero therapy. Now we turn to efficacy, beginning with the dose escalation results on slide number 10. In October 2024, we presented initial results of the triple meeting in Barcelona for twenty five patients enrolled in the dose escalation, of which nineteen were efficacy evaluable. At ASCO, we present efficacy data on twenty eight patients enrolled in the dose escalation. These patients demonstrate a confirmed ORR of sixty eight percent and a disease control rate of ninety three percent with strong efficacy across all dose levels.

Of the nineteen responders, ten ten remain in response between two point eight and nine point one months. So half of these 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 eighty nine patients treated as of April 1, ’70 ’4 pay patients have had at least one post baseline tumor assessment.

The ORR remains quite robust at sixty seven percent in second line patients with a disease control rate of ninety seven percent and decreases not unexpectedly in later lines. Twenty nine of the thirty eight responders remain on study with the longest surpassing nine months on treatment. The median follow-up of this group is three point four months, and the median duration of response cannot be estimated. Interestingly, eighty seven percent 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 thirteen ten in a second line setting.

Across all dose levels in a second line setting, unconfirmed ORR was sixty seven percent. Even more impressive were the results from the one point six milligram per kilo arm where patients achieved an unconfirmed ORR of seventy nine percent and a disease control rate of a hundred percent. Together with a favorable safety profile, these data would support one six one point six milligram per kilo as a reasonable phase three dose pending the completion of dose optimization, longer follow-up, and discussions with the FDA. The waterfall plot on slide 13 includes the seventy four efficacy evaluable patients treated across all dose levels, demonstrating eighty nine percent of patients experience a reduction in their tumor burden. Interestingly, fifty five percent 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 metastasis with a median time to response of five point six weeks. In addition, frank progression is rare, and some patients continue on study past eleven months.

In second line patients treated with Zosi, 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 forty eight weeks, and the longest responder at the one point six milligram per kilo dose is over thirty six weeks on trial. Turning to slide number six, an interesting slide. Brain metastases are very common in patients with recurrent small cell lung cancer with up to seventy percent 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 twenty two patients or thirty percent of patients who had either a target or nontarget lesion in the brain at study entry. The ORR of this cohort was sixty eight percent. However, the response in patients without prior cranial radiation was eighty six percent. 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 seventy percent.

While we continue to evaluate intracranial activity in all the patients, we are highly encouraged by the data we observed. So 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 antitumor 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 one point six milligram per kilo 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 three pivotal trial assessing ZL one three one zero 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.

Rafael Amado, President and Head of Global R and D, Zai Lab: Thank you, doctor 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 one point six milligrams per kilogram 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 seventy nine percent, a well tolerated safety profile, and efficacy in brain metastases, ZL-thirteen ten 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 three point four months, we note the longest ongoing response is nine point one months with twenty nine of thirty eight responders still on treatment. Based on these results, we will be initiating a registrational 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 investigator’s choice of therapy. A 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. E 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 twelve 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 three hundred and fifty thousand to four hundred thousand patients. These are aggressive tumors with poor long term survival outcomes and very limited treatment options. We’re aiming to accelerate a Phase onetwo potentially registrational study this year. Together, these programs provide us with an opportunity to expand the reach of CL1310 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.

Taken together, the profile we’ve seen with CL1310, 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 one point six milligram per kilogram dose pending FDA agreement. I look forward to providing further updates on our DLL3ADC program in the second half of this year. And now, operator, please open the line for questions and answers.

Operator: Thank you. Our first question comes from the line of Yigal Nochomovitz from Citigroup.

Yigal Nochomovitz, Analyst, Citigroup: 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 one point six is the right dose to take forward into the pivotal studies? Thank you.

Rafael Amado, President and Head of Global R and D, Zai Lab: Yes. Thanks for the question. We started based on the therapeutic window that we had seen comparing to NPK with one point six. And as as Doctor. 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 with the and below, particularly with 1.6, we only saw two grade one that were able to be retreated. So there is, as you saw in the in the dose response, a slight attrition as you go up with the dose. And 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. And so if you look at also a a hemorrhagic toxicity, there, you know, there’s a difference where we only saw a six percent grade three plus with one point six. So you’re right.

The therapeutic window may still be narrow, but we have what we think is is an a good dose at one point six. We’ve been asked to study a lower dose, which is not unusual. FDA often does that, and we are putting patients in one point two as well. And then we will very carefully look at these patients and make sure that they’re measuring up both efficacy and safety wise with one point six. And as we announced, we got fast track.

We will we will also apply for VTD and hope to have a pretty fluid dialogue with FDA to to be able to land on on that dose. So, I mean, so far, it appears based on the totality of the data that particularly in second line, one point six is highly active with actually a very mild safety profile, particularly when compared with other AGCs and other classes. So so that’s what I can say as to where we are now. We we will complete the the randomization and expansion and then present the entire package with some durability to FDA and make the decision. And we hope to do that before we start the phase three.

Yigal Nochomovitz, Analyst, Citigroup: Okay. Thank you very much, Rafael.

Operator: 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.

Yigal Nochomovitz, Analyst, Citigroup: Hi. This is Albert Agustinos dialing in for Jonathan Chang. Thank you for taking my questions. So 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?

Rafael Amado, President and Head of Global R and D, Zai Lab: Yes. So as you know, there’s there’s been already precedence of ABCs, supplanting chemotherapy in other diseases, and, you know, some of the very effective ADCs out there are moving into frontline as well with chemotherapy sparing regimens. We wanted to be methodical in terms of combinations. Cisplatin ethoposide is is active, and it’s active fast. So in order to to be able to discontinue chemotherapy and just use checkpoint inhibitors plus thirteen ten, we have to demonstrate a combinability, but also that the activity is competitive and superior to the standard chemotherapy regimen that that’s available now.

We we are confident that that will be the case because in second line, we are seeing numbers that compare very favorable with chemotherapy upfront. And what I can tell you is that we are finishing the atezolizumab combination and have started the carboplatin combination along with atezolizumab in frontline patients, and we will expand that as well. You know? And as the field evolves because of the entrance of new agents, like the T cell engagers, we will explore as well, you know, the possibility of combinations with T cell engagers if those end up being, you know, part of the frontline regimen. But our our initial going in is is that probably the frontline combination will include carboplatin, Adezo, and thirteen ten.

So that’s that’s that’s where we are now. We will continue the dose escalation and and and collecting efficacy data and safety data. So far, the safety has been unremarkable, and the efficacy has been quite good. And we’ll make a decision after we collect all that data. And meanwhile, we’re really focused on the second line.

Yigal Nochomovitz, Analyst, Citigroup: Got it. Thank you.

Operator: Thank you. We’ll now move on to our next question. Our next question comes from the line of Anupam Rama from JPMorgan. Please go ahead. Your line is open.

Priyanka, Analyst, JPMorgan: Hi, guys. This is Priyanka on for Anupam. Can you quickly put the durability of ZO thirteen ten into context with the competitive landscape of the refractory SCLC?

Rafael Amado, President and Head of Global R and D, Zai Lab: The the follow-up, as Doctor. Patel mentioned, is is not very long. That’s why we isolated the dose escalation because that’s the one that has the longest. And just to reiterate what you heard, the median follow-up for that group of 28 patients was six point nine months. The response rate was sixty eight percent.

So that’s mature response rate. Everybody is confirmed, and the disease control rate is ninety three percent. This is across lines of therapies. And we have still 10 patients remaining in response. So, you know, just above fifty percent, fifty three percent, and half of those responses are at six months or above.

So with that median and the number of patients still in response, you know, that can give you a sense of, you know, what that durability may be at least in that in that group. You know, the durability of other agents in this class, you know, whether it’s 5.7 or lower response rate, but durability more in the nine months with TCEs. So for us, I think, you know, durability is around six or above would be would would be considered clinically meaningful. And for the rest of the patients, the of the the entire seventy four patients for whom we have efficacy, the follow-up is three point four months, and and the median has not been reached. But if you look at the, you know, waterfall plot, you can see that, you know, many of these patients are continuing are close to thirty percent, are still early in the study, and and the the response and durability, know, will continue because many of them are still continuing to be treated.

But we can unfortunately give you a number now, and it just we just have to wait. And obviously, the longer, the better.

Operator: 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.

Michael Yee, Analyst, Jefferies: 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, pirilatumab, 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.

But maybe you could compare and contrast those two and particularly the opportunity in first line for both of these agents given Tarleva versus this ADC? Thank you.

Alex Spiro, Director of Clinical Research and CEO, Next Virginia, co director at the Virginia Cancer Specialist Research Institute: It’s Alex, Spiro. So I mean, I just pulled up the New England Journal article this morning. So, you know, Tarle is a great drug. You can’t belittle it at all. The challenge is in the The the clinical trial obviously was a very selected site.

And 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 big academic centers, can’t really do it that well. I mean, obviously I’m a researcher, and I do a lot of things, and even our hospital can do it and can administer it, just because of logistical implications, hospital reimbursement, etcetera, plus all the toxicity. It’s obviously a good drug, but 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 TARLA gets to be administered as an outpatient and certainly Amgen is finally studying it, it’s the significance of cytokine release syndrome and ICANS events that happen at all hours of the night, making it challenging to give in an outpatient scenario. So I think it will largely be used because of ease of administration going forward.

And certainly you didn’t ask the question, but 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.

Yigal Nochomovitz, Analyst, Citigroup: Thanks, doctor.

Rafael Amado, President and Head of Global R and D, Zai Lab: Thank you.

Michael Yee, Analyst, Jefferies: Would I

Rafael Amado, President and Head of Global R and D, Zai Lab: would just simply add that, there are, you know, different mechanisms of action. And even though selinexol, we’ve, I think, treated up to four patients post cerdulatinib, And, you know, we’ve seen a complete response, a partial response, and some decrease in in tumor diameters in in a couple of other patients. So you know? And there there will be combinations between ADCs and and this modality, I think, as as people started, you know, sort of working out how to treat this disease. But, you know, the the there are clear differences in in toxicity, although it’s it’s a highly active drug as you saw.

Operator: 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.

Priyanka, Analyst, JPMorgan: Hi. Congratulations on the data, and thanks for taking my questions here. I wanted to ask you, what gives you confidence in a potential accelerated approval for z l thirteen ten? And and what do you think the FDA needs to see for accelerated approval?

Rafael Amado, President and Head of Global R and D, Zai Lab: Yeah. So we’ve we’ve been having discussions with with FDA about this potential. They have been unambiguous about the fact that axillary approval is an option in the context of of the randomized trial that we described earlier and that, you know, that would be based on comparisons of response rate. So I think the the agency and us are discussing what the numbers should be between, you know, both the control and the test arm. They obviously do want every patient to be approved by the time the analysis is done, and they don’t just want the number of patients.

They want them followed for a period of time, probably around eight months or so. You know, that number of patients, you know, would probably be around a hundred per arm. So, you know, we think that we could have that data in 2027 on file. So we don’t expect the agency to change its mind. Obviously, there will be an approved drug with full approval, but I think they they really realized that we need more drugs in this disease, that this is a different mechanism of action, you know, different ease of administration.

And we’ve received no signal that, you know, accelerated approval is a viable option for the drug.

Priyanka, Analyst, JPMorgan: Thanks. And I have just one quick follow-up question. What do you hope to see in your combo data later this year, and any positive read through from the data today to that data coming up?

Rafael Amado, President and Head of Global R and D, Zai Lab: I think it’s early day for the combo data. I mean, it’s all the patients are responding, and, you know, their responses are high. And, you know, what we expect is that, you know, we’ll see upwards of seventy five percent or so response. And then, you know, we’ll obviously have to have sufficient number of patients and sufficient durability, you know, to to make sure that that that study would be positive. So we also will have to do some dose optimization, although the the companion dropped her and the doses are fixed.

We don’t think that we will have to do as as many doses as we did with monotherapy in second line, so it will go a little faster. But, you know, time to progression will be important. I think, you know, we’ve learned today that it’s in the force or so for terlatumab. So, you know, we will be waiting for, you know, a period of time of, you know, seven months or so to see whether you know, what percent of patients are still in response. So it’ll take some time.

We hope to be able to show some data towards the end of the year, but we will wait until we have a a clinically meaningful data set that’s informative.

Priyanka, Analyst, JPMorgan: Thank you.

Operator: Thank you. We’ll now move on to our next question. Our next question comes from the line of Lee Wotzek from Cantor Fitzgerald.

Lee Wotzek, Analyst, Cantor Fitzgerald: I wonder if you can just talk about the remaining items that you still have to align with FDA before you initiate the pivotal study. Is it just the going forward dose? And then just curious, is there a dose de escalation protocol for the Phase III trial? And then can you clarify if you expect to enroll patients maybe pretreated with tau TALA into the trial just given you require only one prior line of therapy? Thank you.

Rafael Amado, President and Head of Global R and D, Zai Lab: Yeah. All all very good questions. And, you know, some of them, we still need to agree with FDA. It’s a second line study, so these patients will be tirlatumab naive. Now in the control arm, the question is whether tirlatumab will be required.

The FDA has not asked us to to include it. And, you know, there are other studies out there for ABCs where they only include a single chemotherapy. We plan to include dealer’s choice with three chemotherapy. There will be dose modification guidelines for patients that, you know, have toxicities that call for resumption of the drug at a lower dose level. We hope that that won’t be very high because, you know, we have we have seen that in very few patients, so a one point six, if that ends up being the the final dose.

I think the important the most important thing is to land on the dose. We we plan to update FDA on where we are with the totality of the data soon, and we’re putting that together and then understand from them what else, if anything, is required for us to to choose the dose. And, you know, if they if they ask us to increase the number of patients or or, you know, any other variation, then then we will complete that. Accrule has not been an issue for us, and so we think that, you know, we’ll we’ll we’ll be able to have those data available before the initiation of the study. Of course, you know, the sooner we can we can do it, the better.

But that that is really the main, you know, the main issue with regards to what’s left with with FDA in terms of agreeing on the study design. And, yeah, the issue of tirlatumab hadn’t come up. I’m sure it will come up in the next discussion. And tirlatumab is unfortunately not approved in many countries. So patients in The United States may see tirlatumab.

But, overall, the use of tirlatumab, if we start the study soon in the control arm, we don’t expect it to be overly high.

Lee Wotzek, Analyst, Cantor Fitzgerald: Okay. Thank you.

Operator: 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.

Yigal Nochomovitz, Analyst, Citigroup: Hi, thanks for taking my question. Congratulations on great data. I have two questions. First one question is about, can you elaborate more on the ILD occurrences, particularly on the two grade three and above IOD cases? What are the those levels for those two cases?

And, 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.

Rafael Amado, President and Head of Global R and D, Zai Lab: Yeah. Good question. And I’ll I’ll focus on those two grade three and above. One one was a grade three patient, and the second ended up being a grade five patient. I think as Doctor.

Patel mentioned in his remarks, the patient was initially treated and then withdrew treatment. You know, the the thing about ILD is that it it it requires some time to for it to manifest. So we had treated a number of patients at doses at two and above. And and then we saw these these two events at two, and the other one was at two point four. Relatively, you know, sort of, you know, concomitantly on time.

And, you know, that’s what led us to, you know, institute guidelines for follow-up for these patients. And that you know, the more you look for this, the more you see it, obviously. So we’d review the scans for fibrosis very thoroughly prior to patient centering. We’ve learned that patients that had, you know, high doses of fibrosis of radiation, for instance, above 35 gray or 40 gray are at higher risk. And then, obviously, dose is is a factor.

And then be very vigilant with questioning the patients and performing CAT scans. And if we see grade one, then stop immediately and then resuming when the patient recovers. AGC is seen is there are all of them associated with ILD, and I think, you know, this we just have to be vigilant about this. So I I would just, you know, sort of echo that it’s been seen as well in in, you know, with b seven eighty three. And, also, our study was multicenter and multicountry.

So, you know, when you have multiple centers, patients with multiple lines of therapies, etcetera, you know, you may see this more often. But in general, you know, we don’t we don’t think that high grade ILD is any different than anything that’s interesting with other ADCs. I don’t know, Doctor. Spire, if you want to comment about your experience with ILD and ADCs in this field.

Alex Spiro, Director of Clinical Research and CEO, Next Virginia, co director at the Virginia Cancer Specialist Research Institute: Yeah. I mean, you you said it very well. The bottom line is it happens with all ADCs, especially in lung cancer patients. You know, anybody who may have changed, but, obviously, lung cancer patients that have been treated before with radiation to 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.

And it will it does take investigators and physician diligence to monitor closely for signs and symptoms. But in the studies we’re all used to it and clinicians are used to it as well. Again, 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.

Rafael Amado, President and Head of Global R and D, Zai Lab: Yeah. And as I said before, it doesn’t manifest right away. You know, it it generally takes about sixty days or so. You know, a number of patients at 1.6 have passed that that threshold, and we’re not seeing very many. We just see a couple of them with grade one.

So so 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 of interstitial lung disease.

Operator: Thank you. Got it.

Rafael Amado, President and Head of Global R and D, Zai Lab: Thank you.

Operator: There are no further questions at this time, so I’ll hand the call back to Rafael.

Rafael Amado, President and Head of Global R and D, Zai Lab: Thank you, operator, and thanks to everybody that were on the call today. We will be presenting the poster later on today. Again, thank you for your attention. And operator, you may disconnect.

Operator: Thank you. This concludes today’s conference call. Thank you for participating. You may all now disconnect.

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