Welcome to today's IGCS webinar, Emerging Data in the Platinum-Resistant Advanced Ovarian Cancer, which is supported in part by ImmuneGen. IGCS is committed to providing meaningful opportunities to our industry colleagues to gain exposure to our gynecological oncology community through the Advances and Updates educational program. This program provides the level of strategic engagement and exposure needed to educate and inform gynecological oncology professionals on current and future therapeutics to optimize patient care locally and globally. I'm David O'Malley from the Ohio State University and James Comprehensive Cancer Center, where I'm honored to lead the Division of Gynecological Oncology. Within the GOG partners, I also help lead the ovarian cancer portfolio. I am joined by my very good friend Dr. Lainey Martin, who her and I go so far back on some of these ADCs. It's so cool to have her here. Dr. Martin, please introduce yourself. Hi, my name is Lainey Martin. As Dr. O'Malley said, I am an associate professor in the Division of Hematology Oncology at the Hospital of the University of Pennsylvania, and I work very closely with my GYN oncology colleagues. I lead the MEDUNC program in GYN oncology and do a significant amount of phase one and early development along with our phase two and three trials. I'm glad to be here. Thank you for inviting me, David. Oh my gosh. And thanks to IGCS. Yes, and IGCS, and thank you all of you who are joining those who will be listening in the future. Before we get started, let's do a little housekeeping here. Please know that a recording of this webinar will be available on IGCS Education 360 Learning Portal within one business day. We encourage you to submit questions via the Q&A feature at the bottom of your screen, and we're going to do our best to address as many questions as possible. And I'm going to keep this at 20 minutes because we're sensitive to everybody's time. Lainey, let's get started. I'm going to start with, I'm going to start here. Okay. Before we can really talk about platinum-resistant ovarian cancer, what are you doing in platinum-sensitive? I mean, platinum doublets, are you utilizing part mains or utilizing mains in general? Yeah, absolutely. So I feel like I'm giving ever more platinum doublets, even third and fourth line nowadays with the maintenance therapies that we're using that are really enhancing the PFS for our patients with platinum-sensitive disease. So I do believe in platinum doublets for patients that are good performance status, and I generally do offer maintenance therapy in the recurrent setting generally with Avastin. How about you, David? Are you doing a lot of maintenance? Well, you know what? I do. Why don't we pull up the survey? So we asked the participants here, and about 63% of patients are using, people, excuse me, are using maintenance therapy all the time, and occasionally 24%. So 85% are using some mains. You know, I think as we look at the prospective data and placebo control being 5.5 months, the conversation I have with patients is you now have recurrent cancer. Getting rid of it so it doesn't come back is not a realistic option. What we're going to really talk about is maintaining control for, I hope, many, many, many years. And by using maintenance or well-tolerated therapy, and you know, with so much PARP in the upfront setting now, for me in my practice, I'm using a lot of Bev in the in the platinum sensitive space, and trying to extend out that, hopefully keeping them from having symptoms. But you know, one thing that I haven't started doing is really looking to change up from a platinum doublet. I know a lot of people ask me, you know, what happens if you have a patient that has a high folate receptor alpha? Are you changing? I'm with you. I'm still using platinum doublets. So, one thing that you and I have talked a lot about is when are you doing your tissue? Well, what tissue test are you doing? Because gosh, a lot of things have changed in the last 10 years. So, what tissue test are you doing, and when are you doing it in your ovarian cancer patients? Yeah, I mean, it's so important to get that HRD and BRCA information up front, but I like using an assay now and have been using an assay where I get all of the information that is meaningful right now. So, I'm getting that folate receptor alpha testing, you know, often at frontline because it's one molecular test in the somatic setting. I'm not having to then reorder something at recurrence. You know, you have the rare patient that maybe had just BRCA or HRD somatic, and then those I'm tending to order a bigger panel at first platinum sensitive recurrence so that I just have that information and I'm ready to go. What about you, David? Well, yeah, I'm with you. I'm ordering HRD and germline up front on everybody. Absolutely. Now, what else? Again, some of the commercial vendors were not able to get this NGS as well as folate receptor HER2. I mean, I want all of that up front so I know that information and when, if or when they recur, the patient recurs, that we have that information with regards to sequencing, with regards to clinical trial. So, I'm trying to get all of that up front. If I don't get the NGS and the IHC, the immune histochemistry for folate receptor alpha, as soon as they start to, their CA125 starts to creep up, I talk to them about getting that testing at that time, even in the platinum sensitive space. I'm not waiting for platinum resistant because I want to know that data as we move forward. You know, so we're having, we're all, we're both trying to get that data as soon as we can, okay? How about, you know, how about for patients around the world who may not have access to some of this testing? I mean, what are your colleagues, as you've talked to people around the world, are they utilizing the same things that we're doing in the U.S.? Yeah, I mean, that's a good question. I think it depends on, you know, there are a lot of pathways that we're all using in the U.S. and globally, and they often do more hierarchical testing, you know, because they're often paying sort of for the individual tests, whereas here in the U.S., I think most of my colleagues that I've talked to are doing these big panel tests because you get one bill, you order one test, you get one billing. So, I think with the hierarchical testing or the, you know, you do often wait till that platinum resistant recurrence to do some of this testing for some folks outside of the U.S., but I can't speak to everything. What are you hearing? I mean, I think it's dependent per country, per region of the world. You know, for me, whenever that, when that testing comes available, utilizing it so you have that information so you can treat your patient with the best therapy. So, speaking of that, we're already 10 minutes and I can't believe this. Oh, my gosh. Okay. I apologize. Okay. So, why don't we put this, the first case up? So, you know, we're all trying to get folate receptor alpha right where we both are. I don't know who we is. Okay. So, this is the case that we, that they win. So, this to me is pretty straightforward, but tell me if I'm losing my mind here, Lainey. You sure have told me I'm losing my mind a few times over the years. So, please tell me if that's the case. All right. So, platinum resistant, folate receptor 80% using the two plus testing, two prior platinum-based regimens, taxane, and a gem, a gemcitabine, and has recurred within four months of the last platinum therapy. What are you doing for this patient? Yeah, for me, you know, I think mirvotuximab is the most effective treatment in patients like this with that folate receptor high expression in the platinum resistance setting. You know, we have that mirosol presentation by Katie Moore at ASCO last year that showed a survival benefit, which is, you know, this is a poor prognostic group of patients, and to see a survival benefit in platinum resistant to me, that is the choice. And they have that data here. They have that folate receptor one result. Initially, when I looked at this, I was like, oh, do they not have the folate receptor? But it's right there. So, it is interesting to see some of these other treatment regimens being used so heavily. What are your thoughts, David? Well, my, so this is, you know, I've really over the years started going much more back to platinum doublets until, until they've shown to be refractory to platinum. So, in this scenario, I would have a conversation with the patient about going back to platinum. And now, if they had a complete response, CAT scan was clear, C125 was normalized, probably would go back to platinum here. And then, though, in this scenario with the high folate receptor expression, you know, which is 75% higher, I would, I would really talk to them about, about utilizing MIRV. You know, there's going to be more and more data that's coming out in this group of patients. And obviously, Mirasol is fantastic. You know, MIRV, Bev, when do you use Bev with MIRV? So, 28% said they'd use MIRV, another 12%. So, 40% would have a MIRV-based regimen. When are you adding, adding Bev to your, to your MIRV therapy? Well, I think I really like to use MIRV at first, platinum-resistant recurrence, and I would consider this platinum-resistant. So, I would be giving MIRV with Bev here. You know, and sometimes we reuse it. So, it was interesting in that last question, you have a lot of people using maintenance, which is probably Bevacizumab, and a lot of people here are still getting Bevacizumab and carrying that through, which, you know, I think is reasonable. I don't always do that depending on the tolerability, but do you, are you a person that carries through that Bevacizumab sometimes through multiple lines? Yeah, you know, I think it's one of the things with utilizing more Bev in the platinum sense of space. You know, I'm, you know, you can only do Bev for so long before you have, you know, issues of proteinuria and renal dysfunction and, you know, blood pressure we can handle usually, but the proteinuria and as we start to see renal dysfunction. So, I look for opportunities to take breaks from Bev, and if I have a high folate receptor alpha expression, I probably would utilize one of those. Now, you know, with the Forward 2 data that we've done and published now extensively, you know, we see that maybe slightly increased rate, maybe, of overall response rate with the Bev, but really that duration response and progression-free survival seems to be increased like it always does with Bev. So, this would be an opportunity where I may not utilize Bev if they're coming right off in the platinum sense. So, you know, we don't have it here, but platinum plus gemcitabine and utilize it in that group of patients that there are, if I had put them on Bev, and as we said I often do, that with a high expression I may hold off, depending on what their symptoms were and where they were. But again, I'm not saying that these patients aren't platinum resistant, but I will go back to a platinum-based doublet if they've had really good response to their previous platinum, but in this case, the high folate receptor alpha, I'd probably go with the Merv, you know, plus minus Bev. So, I think, you know, it's, so how are you, you know, my patients really, as soon as I start talking about the eye toxicity, they always freak out a little bit. How are you approaching your education to both your patients and then also your treatment as well as mitigation for your Merv, eye associated toxicity? What are you guys doing? Yeah, you just have to really be upfront about it, and, you know, particularly depending on if you have a patient that is still working, they're driving to work, they can't wear their contact lenses, you know, all of this plays a role, so you have to be very frank and upfront that it can cause visual blurring, you can't wear your contact lenses, and it's hard to predict who's going to have that problem. You know, obviously you tell patients you're going to be monitoring closely, it is reversible, and there are dose modifications that can be done, and it's rare to have a very serious ocular toxicity, so that's reassuring, but I do have some patients that say, let's save that one until another time, but most patients are pretty accepting that they're going to get close monitoring, and when I talk to them about the efficacy, they're open to it. Well, and that's, you know, I always learn things from you, Laney, for 15 years I've been learning things from you, and I just, I love what you just said. I have a patient who's still working full-time, who's driving back and forth to school, or to work, excuse me, you know, I think that that is, that's such an important aspect in the education. I don't usually ask that, you know, what I say is, listen, it's very predictable, it's cycle two, day seven to 14, it's reversible, so far we've seen 100% reversibility, people do not lose their sight, we have mitigation strategy in place, but up to about a third of patients, plus minus even up to 40%, will have some sort of eye toxicity, and so to your point, being very open and honest, that we have things which can help, this can be disruptive at times, but for the most people, if they understand that it is, they may have, you know, some difficulty reading at night, I hear that often, hey, I used to read at night, but I avoid that now. So, I think as we look at those, it's 100% reversible, only 1%, not even 1% actually, in the entire totality of the clinical trials, actually stop therapy for eye toxicity, which is pretty amazing, when you think about as much as we talk about and worry about it, that less than 1% of patients stop therapy because the eye toxicity, and 100% reversible, but again, a great thing to bring into, you know, what are they doing, what are they need to do, and if they're really worried about the eye toxicity and the blurred vision, how could that be impactful. So, on that, so this is one of my favorite things to do, which is, and it just got asked in the question and answer, so next case. So, now it comes back and it's 50%. So, you've got a platinum-resistant, let's just say, it's a very similar scenario. This case, though, they're a little bit more heavily pretreated, because they also then had weekly paclitaxel with Bev, but had progressive disease. So, what are you doing for your less than, that less than 75%? Yeah, so, you know, you talk about platinum sensitivity, and I really kind of think about this folate receptor expression and sensitivity to MIRV as a continuum, and, you know, we have the forward one study, which was a negative study in terms of, you know, it was anticipated to show superiority to chemotherapy, and, of course, the biomarker, there was an attempt to simplify that biomarker, and it didn't really select a third of those patients were really less than, you know, less than 50%. But when you look at sort of the forest plot, there were over 100 patients, a third of patients had this 50 to 74, and, you know, the MIRV toxamab was at least as good as the investigator's choice chemo arm. So, you know, I think we have to be cautious what we say, because, of course, there are different approvals, and in the United States, it's really only got FDA approval at that 75 and up. But, you know, I think, depending on what's going on with your patient, their candidacy for some of the other things, I definitely, for someone that is, you know, in that 50% and up range, would have a discussion that it might not work as well, you know, as if they had a higher level of expression, but it's reasonable to think about it. And, you know, we have data also from that forward two study that you worked on with that MIRV toxamab-Bevacizepib combination that included those patients with very similar, you know, a little bit lower response rate in that 50 to 74%. But do you use it, you know, outside of the FDA indication in this type of patient? I think with the forward two data, you know, MIRV-Bev was one of the cohorts that I had the honor of leading that, the forward two trial. And so when we look at this, you know, the response rates to your pointers is as good as we have in anything, you know, weekly paclitaxel, Bev, you know, in that same level. So when we're really looking at that with a better tolerated, not a weekly regimen, you know, NCCN guidelines word it very interestingly. And I believe you're on the NCCN now, right? Correct. So, and I was on it for almost 10 years, but I wasn't there when they, then they labeled this. I don't want you to break any confidence here, but, you know, it's labeled, it's written very interesting. It's folate receptor alpha expression. It doesn't say high, doesn't say it just says with expression and MIRV and MIRV-Bev are both listed within the NCCN options as 2A. So I think as you look at, I think 2A, maybe 2B, 2A, as you look at that, you know, for me, if I have a patient who I think is a good cant for Bev, I'm going to use Bev. And if I have a patient who's 50 to 75 and they have utilized other, you know, many other of the platen-resistant Q, 100%, it is just as good as weekly papotaxel probably. And it's better than anything else we have out there. And again, you referenced forward one that, you know, it's a great example that it's another option, which is available for a patient who has good performance status and is interested. So for me, my specialty pharmacist asked me today, how low is too low? How low is too low? I don't go below 50% much, but you're right, it is a continuous variable. It is not a discrete variable. So, you know, 49, 45, where's that slippery slope? I'm not sure, but I tell you 50 to 75, I have zero, zero apprehension on using it with counseling with the patient. So while I cannot believe 20 minutes went by so quickly, I could talk to you all evening with this and so exciting. But that's all the time we have today. Thank you for all attending and thank you to Immugen for supporting this webinar. Thank you to IGCS for having Lainey and I, one of my best friends in GYN oncology, in medicine, I guess, medical and GYN oncology. Thank you for taking the time to listen to Dr. Martin. I always learn from you and thank you for being on tonight. I want to thank IGCS for inviting me. For the audience questions, you let us right into the topics that we are all thinking about right now. Really excited for the future and, you know, even better options for our patients and, you know, have a great rest of the evening to all of you. Thank you, David. It was great talking with you. Thank you. The recording of today's session will be available in the IGCS Education 360 Learning Portal by the end of the week, hopefully within a day or two. We wish you continued health and safety. Thank you, everybody.

Emerging Data

Platinum-Resistant Advanced Ovarian Cancer

Gynecological Oncology

Platinum Doublets

Maintenance Therapies

Biomarkers