Good morning.
Hello. This is Martin Wermke from Dresden, Germany.
Good morning, Dr. Wermke . Thank you very much for joining today. Can you hear me okay?
Yeah, I can hear you okay.
Okay, great. Dr.
I believe you do.
You're about to be joining any moment, Dr.
Yeah.
You're about to be there. Okay. It sounds like both doctors are here. Are you both there? Hello?
I'm still here. Martin Wermke.
Yeah, I think Dr. Girard is there as well. Nicolas?
Are you? No? Okay. It's Nicolas . Yeah. Can you hear me?
Yeah, okay. There he is. Great. Sorry for the delay, everyone. Okay. So, Doctors, I'm going to read through compliance points, and then you can both just say you agree at the end of them. Okay?
Okay.
Okay.
First, Dr. Wermke, let's start with you. First, this call is being recorded and transcribed. Second, you, the expert, attest you will not disclose any confidential or material nonpublic information. Finally, you attest that if you're a physician participating in a clinical trial, you will not discuss information not yet in the public domain. If you're a member of a scientific advisory board, clinical trial steering committee, and/or data safety monitoring board, you will not disclose any information that is not publicly available or any information that will break any confidentiality agreements by which you are bound. Do you agree to these terms, Dr. Wermke ? Dr. Girard, do you as well?
Yes, I agree. Yeah.
Okay. Perfect. As call leader, I too am required to keep any material nonpublic information confidential. I attest that I will not share material nonpublic information or information that will break any confidentiality agreements by which I am bound. Lastly, I'd like to note this call is intended for informational purposes only, not investment advice. The contents of this call, including any and all information provided regarding individual securities and/or institutional accounts, do not include financial, legal, or tax advice. To everyone on the call today, I'd just like to note this call is being sponsored by PharmaMar. PharmaMar is an oncology-focused company that develops therapies derived from the sea and has been developing lurbinectedin for a number of years. This call is brought to you free of charge by them today.
Doctors, I'd like to start off with each of you maybe giving a little bit of background before we get into the number of patients you treat and where you practice. Could you just both tell me if you have any association or confirm that you don't have any association with PharmaMar and the clinical trial in IMforte? Also, there's a little bit of background noise in the line from one of you, so I don't know if there's.
No, I did not participate in IMforte. In France, we have access to lurbinectedin in part of the compassionate use program, but we did not have this trial.
Okay. Excellent.
Yeah. Similar here, I've not been part of the IMforte trial. We do have access to lurbinectedin in the compassionate use program. I do not hold any shares or stuff in PharmaMar. I have been on a few advisory boards for PharmaMar and other companies as well.
Neither of you were in the IMforte trial. You've just done some compassionate use things and things like that.
Yeah.
Okay. Great. To get started, just to maybe give everyone a sense of your background, I know we have bios for you both, but just how many patients, where are you practicing, what type of setting, and then how many patients with also lung cancer are you currently managing? We could each do that, and then we'll talk about how to compare this to trials or think about the trial.
I'm Dr. Nicolas, I'm working in the cancer center in France. We see 600 new patients with lung cancer, advanced lung cancer every year, about 100 small cells. We participate in clinical trials and so on.
Okay. Perfect. And now Dr. Wermke .
Yeah. I'm also a medical oncologist. I work at the National Center for Tumor Diseases in Dresden, Germany. We do have a lung program. It's not as large as Nicolas's. We see about 250 lung cancer patients newly each year. We do have a lot of referrals for clinical trials which are focused on last-line immunotherapies. This is also due to the fact that I'm not only in charge for the lung cancer program but also for the phase I unit. In that function, I have a lot of trials ongoing with many different compounds, also in small cell lung cancers.
Okay. Perfect. Maybe you could continue. I want to get through how you're currently treating patients first line and what you are thinking of how things may change. Maybe just give me a high-level, Dr. Wermke , to start, and then Nicolas, it's you as well on your impressions of the IMforte data, how you think the caliber of the study design and how it was conducted, and just what did you think when you saw the top-line results and the recently elaborated on information. How did that go?
Maybe I can start. I'm quite convinced by the IMforte data. The three-month benefit in PFS and OS is something that is clinically meaningful. This is why we implemented immunotherapy in small cell. Here, we are in another incremental benefit that we see with the addition of lurbinectedin. What I also know from my patients is that only 80% in my center, but maybe only 60% overall in France from real-world data do access a second-line treatment. Having an early exposure to lurbinectedin actually avoids this loss of patients from first line to second line. My point is that given what we have seen at ASCO with tarlatamab, and we know that tarlatamab has also been tested as maintenance, I expect that the magnitude of benefit with tarlatamab as maintenance will be higher.
There is, I would say, a slight timeline for lurbinectedin to be there. We have a compassionate use program in France for second line. Actually, I would like to treat my patients tomorrow with lurbinectedin as maintenance based on the IMforte data.
Okay. Excellent. Martin, yeah.
Yeah, may I add from my view? I think the situation's the same here. We are usually treating our patients with first-line immunotherapy. At the moment, I think it's equally distributed between the atezolizumab and durvalumab-based regimen. I am impressed by the IMforte data. I think, as Nicolas just said, that will change our practice given on the overall survival and progression-free survival benefit observed. It will become a standard for maintenance in the first-line setting, which will probably mean, depending on the burden of the labor, that we will switch to atezolizumab-based immunochemotherapy for first line for the time being. Actually, I also look forward to treating the patients, and I share a bit of—I would not call it concern, but I'm curious on the data of the ongoing tarlatamab maintenance trials, which are ongoing. We don't know what happens there.
We've had a paper at last WCLC showing that that has promising activity. I think at the moment, it's too early to really say if this is then going to replace lurbinectedin or if there may be room for combinations. I don't know. Certainly, the landscape in small cell lung cancer is changing quickly. We're pretty sure that we need to adapt as quickly as things change.
Okay. Great. That's a good start. Girard, I think you touched on one of the questions I had in terms of the current landscape and how many first-line patients are currently able to get to maintenance and then progress to second-line treatment. Could you maybe both elaborate a little bit on that and how you see that in IMforte potentially changing the situation?
No, that's a very good question. In IMforte , it's about 80% of the patients who get to lurbinectedin maintenance. The other ones are early progressors, and this is what we have in the clinic. IMforte is also restricted to patients without brain mets. At the end, from 100 patients with small cell metastatic, it's about half of the patients because you have something like 25%-30% of the patients with brain mets upfront at diagnosis. Then it's 80% of those patients who will go to maintenance without the disease progression. It's about half of the newly diagnosed metastatic small cell lung cancer patients.
Yeah. I think if you look at the data from the IMpower133 trial, I think they even had some in the appendix of the paper. There's even the number of patients who received the subsequent therapy, and it was exactly a little more than 50%. I think there is a great rate of attrition between treatment lines, and that is probably one of the keys to understand the benefit of lurbinectedin maintenance apart from potential immunomodulatory effects and deepening of the early responses. This is certainly something that is important for lurbinectedin as a second-line maintenance, first-line maintenance, sorry.
Got it. Great. That's helpful. I've been looking at some investor comments and some other conversation going on about the trials and people trying to think about IMpower133, which you just mentioned, and CASPIAN. Maybe how can we compare those two trials? I know there's some differences in terms of induction and the maintenance components and things like that. If you're trying to look at the efficacy scene, my understanding is it's not a one-to-one basis. Could you talk about some of the nuances between those three trials and how we should contextualize the IMforte lurbinectedin data that we just got relative to what maybe some other people are looking at before we go on that or a little bit in the incorrect way?
In the first thing, it's always difficult to do these cross-trial comparisons, but here you have to be extremely careful, especially when comparing absolute numbers, given that the survival times in the IMforte trial have been calculated from the date of randomization into lurbi or atezo or atezo maintenance and does not take into account the time that is needed for the induction treatment. So we lose, in that sense, about three months. It's not wise to directly compare the survival times between these two trials. On the other hand, the lurbinectedin cohort is also a positively selected cohort because you lose all these early progressors during the first-line induction therapy. It's really hard to definitely compare it. You can be sure for those patients eligible, it is a step forward, and it is an increase in the survival times that is real and clinically meaningful.
Yeah. Could you maybe just elaborate on that point in terms of not including the first three months? And how does that, I guess, if you were trying to make that comparison across trials, impact the differences in efficacy seen if you were to try and further elaborate?
The way it's difficult to compare.
Translate to?
It's always difficult to compare one trial to another because also of the time needed to select and enroll and staff the patients, especially in small cell, which is a negative disease. Obviously, so I feel that the CASPIAN data have a better quality, longer follow-up as compared to the atezo. I prefer to use durvalumab, actually, right now, but it will change to atezo given the IMforte data. Durvalumab, because of the four-week time interval for maintenance, which is better for the patient and the hospital. It's true also that atezolizumab now is available as subcutaneous, which facilitates probably the delivery. Now that we have IMforte , we will switch back to atezo.
Actually, in terms of efficacy, I don't see a real difference between durva and atezo. And actually, with durva, we have the option to use cisplatin, which I hardly ever do. So I think for me, it won't be an issue to switch to atezo once we have the approval for lurbinectedin maintenance. And going back to the cross-trial comparisons, I think, I mean, IMforte is very clear in saying that if you meet the eligibility criteria, you will live longer by adding lurbinectedin to your treatment. So it's a clear positive trial. And I don't think it's wise to compare any absolute numbers between this trial, which is a maintenance trial, and other trials which started with induction therapy. So it's just an add-on to what we've seen and what we've learned with the immunochemotherapy trial.
Got it. Yeah, that's helpful. Yeah, I mentioned it just because I think some other investors trying to contextualize this have looked to those trials, but I understand the difficulties comparing cross-trials in different formats and designs. I guess, just to put a fine point on the IMforte data, the benefit on overall survival and progression-free survival, you view as clinically relevant and meaningful to the patient journey. Maybe talk about that in context with the safety profile seen and just is that efficacy benefit tolerable in your opinion and something that lines up for the majority of your patients, all your patients? How do you think about this applying across the people you see? Maybe Dr. Girard first.
This is a significant benefit, for sure. Obviously, we pay the price of chemotherapy-like toxicities. At the end, it's really worse because otherwise, the patient, there is a risk that the patient will never get the first line, the second line. All of these side effects are manageable at the end. It's mostly digestive. It's mostly something like hematological, but that's quite easy.
Yeah, I totally agree. I think the toxicity is worth risking because there is a clear survival benefit. Of course, there might be patients not eligible for such a treatment because they're too frail. If you're able to tolerate platinum doublet chemotherapy, you're usually also able to tolerate lurbinectedin. In my view, from the experience we have of the compassionate use program, I usually think it's probably similar to the pemetrexed maintenance we have in non-small cell lung cancer. This is chemotherapy. Of course, it has side effects in terms of hematotoxicity and also some fatigue and GI problems. It's usually a chemotherapy which you can tolerate for prolonged cycles just because it's a pretty mild chemotherapy. That's my perception of lurbinectedin as a drug from the compassionate use program, and I expect it to be the same in the IMforte regimen.
Excellent. Okay. If we could look at some of the, just explicitly look at the side effect profile. The toxicity profile both look very tolerable to you, and nothing that raises concerns from what you're able to manage in patients who are on the line. I have seen a few investors look to that, but not as many as have talked about the efficacy. Just the side effects and toxicities, how do they compare to other options, and how comfortable are you with that treating all your patients?
No, but that's true that there are some toxicities. We know them toxicity quite well in second line, meaning in patients who are the kind of post of chemotherapy in between the platinum and lurbinectedin. Here, we will have to also manage those patients who just received platinum-based chemo, maybe some remaining toxicities, and we'll start directly to lurbinectedin.
Yeah. I agree.
Excellent. Okay. Great. In terms of trial design, we've mentioned that it's different than IMpower133, CASPIAN. How do you view the trial design overall? Does it answer your questions, and do you think that it's a strong, well-designed trial? How do you feel about IMforte as a?
First of all, I think it is a well-designed trial. It has relevant endpoints. It has hard endpoints, and it has a clear structure with the randomization, and it really answers the clinical questions. The only issue I have with the trial design is the exclusion of patients with brain mets, as Nicolas just pointed out. I mean, that excludes a relevant portion of the patients, and I do not really see the rationale why they have been excluded. I would not have done it that way because we do not have any reason to believe that lurbinectedin is increasing any CNS toxicity that might be expected. Why not give it to these patients as well? If I was to design the IMforte trial another time, I would probably skip that exclusion criteria.
If you take that away, I think it's a pretty well-designed and a pretty strong trial giving a clear answer to a clinical problem.
Yeah, I agree. The design is pretty straightforward. Easy to understand. We have PFS. We have OS. That's very clear. And we have not seen that for long in small cells. So that's good.
Okay. Great. Before we get into how expanded access is hitting or infecting things in France and how you're thinking about everything, if it was approved today, how do you see the uptake in Germany? How do you see this working into your practice, and how aggressive would you be in rolling it out?
Yeah. I think in Germany, it will be easy to use that. Usually, we get with the approval, we have market availability, so I can prescribe it tomorrow if it's approved today. I think the uptake will be fast because it's a simple chemotherapy. Every oncologist knows how to do that. You do not need any special precautions, no changes in your practice setting. You can just incorporate this into your infusion department, and everything will work as usual. I don't expect there will be any difficulties in terms of reimbursement later on. I also think that the odds are high that this will get a permanent reimbursement given that we have an adequate comparison arm, that we have a relevant setting, and a hard endpoint. I don't think that there will be too many issues in uptake of this new option.
Excellent. And.
Expansion in France is a very expensive program in France.
Expansion in France. Yeah. How does the expanded access program and the 4,000 patients in it impact how it can be used and how you think it'll roll out in your country and your practice?
No, I think it will be very, very easy because everyone knows lurbinectedin as second line. We see the benefits. So many people will be willing to start and so eager to have an early access program, for sure.
Okay. Excellent. I have a few questions coming in from my colleagues, but just to maybe put a final point on it, if you could each walk me through what you see the sequencing from kind of diagnosis to the full treatment journey for a patient. Dr.
No, but it would be very important.
From the diagnosis through. Now, if you had this approved today and the IMforte data was within the label and available to you, how would you view it, first, second, third line in maintenance and things like that?
Yeah. I mean, the usual or I can easily paste it into my routine practice. Usually, we start with the diagnostic work. We will include a brain MRI scan at baseline just to know if there are pre-existing brain mets. We know if we have a patient that fits the label of the lurbinectedin maintenance, we will probably switch to carboplatin, etoposide, atezolizumab as first-line induction treatment. After we've proven that the patient is not progressive after the first cycle, we will include them into the IMforte regimen and treat them. I don't think that lurbinectedin as a second-line drug will play a role for most of the patients then. Of course, it will play a role for those patients who started their maintenance before availability of lurbinectedin as a maintenance treatment.
What happens when we will have an approval or more data for a tarlatamab-based maintenance, I don't know. At the moment, my sequence will then be maintenance with lurbinectedin until disease progression or intolerability, and upon progression, then switch to tarlatamab second-line treatment.
Okay. Excellent.
I agree. Yeah. Same for France. Exactly the same.
Okay. Perfect. You mentioned tarlatamab. We actually had one of my colleagues who had sent in a question on that as we look at potential first-line competition between lurbinectedin and tarla. Do you think that tarla needs to have the same level of efficacy or potentially a higher bar given the risks and precautions associated with that drug? How do you think evaluating that data or that competition will be on an efficacy basis given the profiles of the two therapies?
Actually, tarlatamab-based is better tolerated than lurbinectedin based on the DeLLphi-304. I don't feel that there is that much of an issue. Tarlatamab is better tolerated than chemo because the safety side effects are actually related to CRS , which is not really an issue. On the contrary, with chemotherapy including lurbinectedin, we have more side effects. From a patient standpoint, I believe that the safety of tarla is better.
Yeah. I can work on that.
I do agree. I think the issue is also that with chemotherapy or not with tarlatamab-based, you have most of the problems in the beginning. Once you pass cycle two, usually, this is easygoing. I see a bit of a problem in uptake of tarlatamab for the first infusions, not at the big hospital centers, but at least in Germany, we have a lot of private practice oncologists. For some of them, it will be challenging to find a way how to safely administer the first infusion of a bispecific T-cell engager. I'm sure with time, there will be solutions for that, so collaboration between bigger hospitals and smaller practices. That might, in the beginning, limit an uptake of tarlatamab if this were to be approved as a maintenance therapy as well.
I agree with Nicolas that if you have both options, I feel that most patients and most practitioners will probably opt for tarla. At the moment, we don't have the positive trial. I would rather wait for this to occur before I draw a final conclusion.
Right. Of course. I think the question was just if that first dose would raise the bar of efficacy, but I understand. Touching on something you'd mentioned in the trial design, considering patients with brain mets at baseline were excluded, would you prescribe this regimen to those patients? It seems like you had mentioned, Dr. Bremer, that you didn't see any toxicity issues with the patients who had brain mets. So would those be patients you would still include or potentially treat with this regimen if it was allowed or if it was available?
Yeah. I mean, if I would be allowed to, I would do so. The problem is I feel that the label will be pretty strict because nowadays, the labels are usually referring you to the inclusion criteria of the studies. If they do that in the SmPC for lurbi in the IMforte regimen, then I will not include any brain met patients just because I fear that the insurance companies will not pay for it. That is probably an issue, and I have seen it. I mean, with the neoadjuvant immunochemotherapies in non-small cell lung cancer, we are strictly following the in-and-exclusion criteria of the trials just to make sure that they are not charging us with the cost for the checkpoint inhibitors. I expect the same to happen here. Short answer, I do not.
From a clinical standpoint, you wouldn't have any hesitation? It would be.
Yeah. No limitation from a clinical standpoint. From a reimbursement perspective, I see a limitation, and I will probably not use it in brain met patients if the label refers to exclusion of patients with brain mets.
I will play with the limit, I think. Small cell is so aggressive that probably some patients with brain mets, minimal symptoms. I will do it. Yeah.
Okay. Great. Another listener had asked about some of the eligibility from a health and frailty standpoint. At the time of diagnosis of ES-SCLC, extensive-stage small cell lung cancer, or after the induction therapy, what percentage of eligible patients are just too frail to receive maintenance therapy? Do you have an estimate on that at the time of either diagnosis or after induction therapy?
I mean, if you are able to receive induction therapy and if you're not progressing on that, if you're not having any septic complications, I think 80%-90% should also be able to receive maintenance therapy at least from the patients I treat. We usually try to deselect those patients who are not fit enough for chemotherapy pretty early on and send them to palliative care in the beginning unless their general status is due to the underlying disease. I don't see that much attrition between the end of the induction treatment and the beginning of the maintenance treatment, at least not for those patients who are not progressive.
I agree because the patients are actually doing better after the fourth cycle if they are not progressive. They are doing better than at the time of diagnosis because chemotherapy is highly effective and improves the general condition of the patients.
Okay. Great. The next last question is just another maybe request to elaborate on the compassionate use program. How quickly can the compassionate use program be adapted to prescribe first-line ahead of a potential European approval? How does that transition look, and how quickly can it go from compassionate use to first-line once it is approved?
I mean, once it is approved, it's available in Germany, so I can switch immediately from compassionate use to prescribing the drug. If you're asking on how fast you can expand the current compassionate use program, which is focused on pretreated patients to the maintenance setting, I'd probably suggest you should ask PharmaMar instead of us. So far, I can say the compassionate use program is pretty well managed. It's pretty easy to get your patients on. After your setup, it's pretty easy to get new patients on. It will be easy to start ahead of the approval of the compassionate use program if appropriately broadened in its inclusion criteria.
From my view, in France, there is no control about the compassionate use program. If I say the patient has a progression, they will believe me. Actually, I will be able to start to do IMforte tomorrow.
Yeah. But then you would have to lie to PharmaMar, right, Nicolas?
No, no, no. I know. No, but I mean, many people will do that. I'm not doing it because I'm at a cancer center, so I have many patients. I don't want to actually play with those limits. It's not good for the company. Discussing with colleagues, they are actually thinking about that. That's the point.
Yeah. Yeah. That's good. I mean, this is staying here. I mean, there's no regulatory oversight for a compassionate use program. So basically, no one is monitoring what you're doing. Of course, if you're working at a center, you will be strictly following the criteria of the compassionate use program.
Yeah. Yeah.
Got it. Okay. Those were the questions that I have here submitted. Maybe we could each just leave or have a moment for each of you to just give a final thought on everything or takeaway and how you think once the IMforte data looks and how it'll be used, just kind of any questions you have or any last thoughts you want to leave everyone with. Maybe Dr. Girard first.
No, but I think this is a positive trial. It's very convincing. The point is the competitive landscape. We know that the tarlatamab maintenance trial has completed the enrollment. If the data are released next year, there will be, at least for the full reimbursement, some competition. The authorities probably will prefer tarlatamab if they have to make a choice with the same timing or even if there is an early access program for tarlatamab maintenance as well. I feel that the time frame and the timeline for lurbinectedin maintenance are quite short, actually, given the competitive landscape, not because of the value of the data.
Yeah. I agree. I mean, this is practice-changing data. It's pretty good to see at a single after-meeting having two practice-changing trials instead of being one of them. I mean, we've had years and years with zero progression in the treatment landscape in small cell lung cancer. It is certainly a move forward. I do agree that it is difficult to judge on what the future of maintenance therapy looks like once all the trials that are currently ongoing have been completed. I do think we need to wait for it because there are many different things, also pricing, side effects, applicability to the broad community that need to be taken into account. It will be pretty interesting to see how the next years evolve in terms of study treatment.
At least for the next one or two years, I think IMforte will probably be the standard of treatment, at least in my country.
Okay. Doctors, I appreciate both your time this morning walking through this. It sounds like very good news for patients with small cell lung cancer. We will have to watch and see how approval and rollout goes for both drugs. Thank you for your time, and have a great day.
Thank you.
Thank you. Bye-bye.
Thank you. Thank you. Bye.
Bye-bye.