Greetings. Welcome to Compass Therapeutics Topline Secondary Endpoints call. At this time, I'll turn the conference over to Anna Gifford, Chief of Staff. Thank you, Anna. You may now begin.
Good morning, and thank you for joining us. My name is Anna Gifford. I'm Chief of Staff at Compass Therapeutics. With me today is Dr. Thomas Schuetz, CEO and Vice Chair of the Compass Board. Earlier this morning, we re-released positive secondary endpoint data from the phase II/III COMPANION-002 study, which we look forward to discussing on this call. The slide presentation accompanying this webcast and a copy of the press release are available on our website. Please note we'll be making forward-looking statements on today's webcast. These forward-looking statements are described in our press release issued today and the company's SEC filings. With that, I'd like to turn the call over to Dr. Thomas Schuetz. Tom?
Thanks so much, Anna. I just want to echo Anna's greeting. Happy to be with you all today, and we're very excited today to discuss with you the initial data from our COMPANION-002 randomized trial. Today we're going to be discussing select analyses of the secondary endpoint efficacy data as well as demographic data and some top-line safety data. The rest of the analyses from the study we look forward to presenting at a major medical meeting later this year. I would also like to echo Anna's forward-looking statement comment. I will be making forward-looking statements today. On slide three is an executive summary of the data analyses so far in our COMPANION-002 study.
Just to reiterate, we hit the primary endpoint in the study of overall response rate, more than tripling the response rate in the control arm, and we presented those data last year. The key secondary endpoint was progression-free survival, and today we're reporting what can only be described as an absolutely stunning result. We have a 4.7 month versus 2.6-month median BICR-assessed progression-free survival with a hazard ratio of 0.44 and a P value less than 0.0001. I'll talk more about that data in a minute. In terms of overall survival, the overall survival analyses were confounded by crossover from the paclitaxel arm to the combination arm. 54% of patients crossed over, and 85% of patients in the study ultimately received tovecimig in combination with paclitaxel.
I'll talk more about that, of course, in detail. Fascinatingly, those 54% of patients who crossed over from the control arm lived an incredibly long time. The crossover patients had a median overall survival of 12.8 months, which is consistent with what you would see in the frontline setting with gemcitabine, cisplatin, and Imfinzi. The patients who did not cross over had a median overall survival of 6.1 months. I'll show all of those data in this presentation. The safety profile was consistent with our previous studies. I'll talk more about that, of course. Importantly, we're now preparing for an FDA meeting in advance of a planned BLA submission. It is our intention to seek full approval.
However, having hit on overall response rate and really dramatically hitting on progression-free survival, we feel at absolute minimum this data set supports accelerated approval, and I'll talk more about that in a couple of minutes as well. Let's just quickly review the design of the study. COMPANION-002 was a randomized trial in patients with advanced biliary tract cancer who had received one prior line of therapy. This is a pure second-line study. It was a two-one randomization of tovecimig plus paclitaxel versus paclitaxel alone. 111 patients were randomized to the combination arm. 57% were randomized to the control arm. In the control arm, after centrally confirmed progression, patients were allowed to cross over and receive tovecimig plus paclitaxel.
As I mentioned, 31 patients from the paclitaxel only arm crossed over to the combination arm to receive tovecimig. Therefore, 31 plus 111, 142 patients in the study received tovecimig at one point during the study. I'll talk more about that in a couple of minutes. On the bottom of this slide is the statistical hierarchy. Overall response rate was to be analyzed first, progression-free survival second, overall survival third. In terms of duration of response, we don't have that analysis today, and we look forward to presenting that at the medical meeting presentation later this year. Let's dive into the data from the study. Let's start with the baseline demographics that are shown here, men, women, and race. You can see the bottom three rows are the most important.
Uh, these were the prognostic variables that were the three stratification factors for the randomization. The first was anatomic location of the primary tumor, intrahepatic cholangiocarcinoma versus other, very well balanced. ECOG performance status zero versus one. You can see those are within single-digit percentages of each other. And then finally, disease status, uh, disease outside the liver or locally advanced disease. The majority of the patients in this study had metastatic disease outside the liver, and all of these three important prognostic variables were well-balanced between the two treatment arms. Just again, an important reminder here that we hit the primary endpoint in the study. All of these analyses were done via blinded independent central review, so-called BICR. So the BICR-assessed response rate was seventeen point one percent in the combination arm with Tovesimig, five point 5.3% in the control arm with paclitaxel.
We had a centrally adjudicated complete response in the tovecimig combination arm. Okay. In terms of BICR-assessed progression-free survival, here are the PFS curves. The red line is the tovecimig plus paclitaxel group, a median progression-free survival of 4.7 months, a median progression-free survival in the paclitaxel control arm of 2.6 months. That revealed a hazard ratio of 0.44, again, with an extraordinarily significant P value of less than 1 x 10^-4. Just a reminder also that we powered this endpoint for a hazard ratio of approximately 0.6. A hazard ratio of 0.6 represents a 40% reduction in the risk of progression, 100 minus 60.
And what we saw was a fifty-six percent reduction in the risk of progression, about fifty percent better than we powered the study for. Let's move to overall survival. This is the intent-to-treat analysis for overall survival. The overall survival analysis was confounded by crossover, and I'm going to talk a lot more about that in one minute, but this is the intent-to-treat analysis. Now, what is most important to understand here is that the quote-unquote control arm includes two different sets of patients. The fifty-four percent of patients who crossed over and received Tovesimig in combination with paclitaxel, and the twenty-six patients who did not cross over and received paclitaxel alone. But this is the intent-to-treat analysis where the patients are allocated to these two curves based on the treatment to which they were randomized.
Again, it's very important to keep in mind here that the quote-unquote control arm is really two different sets of patients, and we're going to talk a lot more about that in a minute. One of the things that we have discussed in the past with all of you is the crossover adjustment statistical methodology. That methodology is called the RPSFT or the rank preserving structural failure time. The rank preserving structural failure time statistical assumptions were not met. You can see that the RPSFT and the intent-to-treat analysis are virtually identical. One of the pre-specified secondary endpoints is an endpoint that we called PFS2. When we saw the intent-to-treat OS curve, we wanted to look specifically at the PFS2 analysis. PFS2 is an analysis of progression-free survival in the crossover patients.
You can see on the bottom left where you see number at risk, 31 and 31, those are the same individual patients. Pre-crossover in red, post-crossover in blue. You can see that there's a significant difference in progression-free survival post-crossover. The patients who crossed over actually had a very rapid initial progression with a median PFS of 1.9 months. After crossing over to receive tovecimig, their PFS improved to 3.5 months. Time zero on these two curves is different. Time zero for the red line is randomization. Time zero for the blue line is time of crossover. Once these patients who had progressed very rapidly on paclitaxel crossed over to receive tovecimig, their progression-free survival improved significantly.
Those two curves are different with a P value of 0.0016 and a hazard ratio of 0.36. Another kind of subtle aspect of this curve perhaps is you can see that there's a rather long tail on this progression-free survival curve. There are many patients here. By the way, this blue curve, of course, is now patients treated in the third-line setting. Many patients here who have not progressed six, nine, and 12 months out after crossing over to receive Tovesimig. That observation led us to do this analysis. This is an analysis of overall survival in the control arm. What we did is we looked back and we split the patients into the crossover patients and the patients who did not cross over.
The patients who crossed over, N equals thirty-one, had a remarkable median overall survival of 12.8 months compared to 6.1 month median overall survival with paclitaxel alone in the patients who did not cross over. Now, obviously, you all know this, and we know full well that when you do an analysis like this, you might have simply selected the patients who were going to do better anyways. And maybe the patients who happened to cross over to Tovesimig were the patients who might have done better anyways. So what we did is we did this analysis for progression-free survival. So as I go to the next slide, just keep an eye on the red and blue curves. For progression-free survival, they are reversed. So the patients who actually crossed over in red actually did worse on paclitaxel than the patients who did not cross over.
Despite progressing much more rapidly, actually significantly more rapidly with a P value of 0.007. Despite those patients progressing more rapidly, I'm just going to go back one slide, they ended up living significantly longer once they cross over and receive tovecimig. We believe this analysis suggests strongly that the addition of tovecimig to paclitaxel is associated with an improvement in overall survival. These slides, by the way, are available on our website this morning. This is top-line safety data. Lots of numbers on this slide. Just want to highlight one number here. The main difference between the two treatment arms is hypertension. Of course, hypertension is on mechanism for a VEGF blockade. There are now published algorithms for managing the hypertension associated with angiogenesis inhibitors. Here's a summary and a brief discussion of our next steps.
The study obviously is positive by definition, with a significant improvement in overall response rate, more than tripling that what we saw in the control arm. For progression-free survival before crossover, there was an incredibly significant treatment effect with a 56% reduction in the risk of progression. Outside of targeted therapies, to my knowledge, this is the lowest hazard ratio on progression-free survival that's ever been reported in this disease. The OS analyses were confounded by crossover, and the patients who crossed over, despite initial very rapid progression, lived an incredibly long time at 12.8 months median. As I said earlier, 12.8 months is the exact median overall survival in the experimental arm of the study TOPAZ-1.
In the front line setting, gemcitabine cisplatin plus Imfinzi has a median overall survival of 12.8 months, and those crossover patients now treated in the second and third line setting had a median overall survival of 12.8 months. A safety profile was consistent with our prior studies, and the drug was well-tolerated. As I mentioned earlier, our next steps will be to meet with the FDA to discuss these data in advance of a BLA submission. As I mentioned earlier, it is our intention to seek full approval based on these data. After a discussion with FDA, we certainly believe that the combination of ORR and PFS supports accelerated approval as it has for many, many dozens of other oncology drugs.
We feel quite strongly about our data because when our data are put in context compared to several different chemotherapy regimens that are used in the second-line setting, such as FOLFOX or FOLFIRI, where one randomized trial was done, you can see that FOLFOX had a 2.8-month median progression-free survival compared to 2.1 months with FOLFIRI, median overall survival is 5.7 and 6.2 months. With our study, the pooled median overall survival is approximately nine months, 50% longer than you see with any chemotherapy regimen in this setting. Significant improvement in overall response rate, very significant improvement in progression-free survival. Overall survival, ITT analysis confounded by crossover. The crossover patients lived an unbelievably long time and just a very, very satisfying observation for us to see how long those patients lived.
Next steps for us, put all the data together, meet with FDA, and discuss the pathway to a Biologics License Application submission. Thanks for your time this morning. Happy to take questions.
Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question at this time, you may press star one from your telephone keypad and a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. In the interest of time and to allow as many as possible to ask questions, we ask you please limit yourself to one question and one follow-up. Thank you, the first question is from the line of Jonathan Chang with Leerink Partners. Please proceed with your questions.
Hi, guys. Good morning, thanks for taking my questions. First, how do you view the efficacy and safety profile of tavasomig plus paclitaxel compared to chemotherapies used in this treatment setting? Just as a follow-up, can you provide more color on the crossover adjusted OS analysis based on RPSFT? How should we interpret those data given that the statistical assumptions for that analysis weren't met? Thank you.
Okay. Thanks, Jonathan. In terms of the first question, you know, of course, you know, When you look at paclitaxel in comparison to FOLFOX or FOLFIRI, you know, fairly similar safety profiles there. You know, the real difference here is again hypertension, which again is on mechanism for angiogenesis disruption. You know, there are now published algorithms for managing the hypertension associated with drugs like Avastin. In the Avastin label, there's language about treating the hypertension rather than discontinuing Avastin, and that's the approach that we took in this study. Your second question is paradoxically very complex and very simple.
The statistical assumptions for the RPSFT analysis were not meant, so the RPSFT numbers that we're reporting here, we're reporting for full disclosure, just for full disclosure, but the RPSFT analysis is meaningless, which is why we presented the IPE analysis on slide eight.
Got it. Thanks for taking my questions.
Our next questions are from the line of Maury Raycroft with Jefferies. Please proceed with your questions.
Hi. Thank you for taking our questions. This is Amin on for Mori. A couple of questions from us. First on, just to make sure we're interpreting the data correctly and using the right comparisons, if you look at the pure tavasomig treated patients versus patients who receive paclitaxel without crossover, looks like the OS figures are like 8.9 months versus 6.1 months. Is that the right way to think about the underlying treatment effect here? I have a follow-up on the FDA interactions.
Yes. That is completely correct. The combination arm 8.9 months, the paclitaxel only arm 6.1 months. Correct.
Okay. Thank you. That's clear. Have you had any regulatory discussions with the FDA in the past few months to see how they view the bar for successful study? If not, when do you expect to have your next discussion with the FDA?
Okay, two-part question. The answer to the first part of your question is no, we have not had any discussions with the FDA in the past few months. The second part of your question, we expect to complete the analyses of all of the other endpoints in the study within the coming approximately 1 month, and then we would put everything together into a meeting request and package and send all of that into the FDA, which should put us in position to have a meaningful conversation with the FDA in approximately the middle of the summer.
Thank you very much.
If that conversation goes well, you know, then that would put us in a position to submit a BLA application, before the end of this year. Because we have a Fast Track designation, of course, that could, you know, potentially put our PDUFA date sort of inside the second half of next year.
Our next questions are from the line of Biren Amin with Piper. Please proceed with your questions.
Hi, guys. Thanks for taking my questions. Can you maybe talk about the influence of drug discontinuations for dose reductions with the tavasomig arm versus pac alone? Then maybe another question. I know Tom, you're not talking about duration of response today, and that's gonna be at a medical presentation, but, you know, what were the data there, and read through on PFS? If you could just maybe tell us, I guess, from a high-level perspective.
Okay. A two-part question. In terms of all of the data for dose reductions and treatment discontinuations, I don't have the totality of that data set today. I did, because hypertension was most common, I looked at that specifically, and there were 4 patients, 3.7% who had drug discontinuation from hypertension. The rest of that data is in process for analyzing. You know, in terms of your second part of your question, in terms of DOR, we did not prioritize that analysis for this presentation. The only thing I'll maybe add to that is, you know, one of the things that was very, very interesting to us is in the PFS2 analysis.
Again, patients who very rapidly progressed on paclitaxel only then crossed over, there are additional responses in those patients after crossover. You know, that's also a very interesting piece of data that we're, you know, scouring through now.
Maybe if I could have 1 follow-up? On the patients that crossed over, were they more or were there any baseline characteristics? Because if I look at, you know, on PFS2, I think you reported, you know, 3.5 months on the patients that crossed over on PFS2.
Yeah.
If I, you know, calculate and add the 1.9 months that they had on PFS1, that gets you to about 5.4 months. Where I'm going with this is, you know, your OS was significantly higher at 12.8 months, compared to the tavasomig arm at 8.9. I think the difference is, on those patients that crossed over. I mean, they seem to have been doing slightly better. Was there anything from, like, a baseline characteristic of those crossover patients?
I don't know the specific answer to the question as you phrased it. We are examining all of the information for those 31 patients incredibly carefully. You know, we're gonna, you know, be in a position to talk more about that. You know, I, you know, I very much, Biren, I think that the caveat that you made here, is quite important, right? You know, we need to make sure that these patients who crossed over, that we're not biased here by selecting a patient population that was gonna do better anyways. That's why we did the PFS analysis on paclitaxel that we show on slide 12. If PFS is a marker here, not only did the crossover patients not do better, they did much, much worse on paclitaxel only.
As measured by PFS, the crossover patients were actually a worse subset, and despite that fact, they lived significantly longer once they crossed over to receive tovesimig.
Perfect. Thank you.
Mr. Weiss, you can proceed with your question.
Hello?
Hey, Tom. Can you hear me?
Yes. Yes. Sorry.
All right. Sorry, everything went silent there for about, a minute or so.
Yes, sorry about that.
Maybe to follow up on Biren's question, do you have much, if any, patient biopsy data? Are you gonna be looking at retrospective DLL4 expression in these patients, I guess specifically in those 31 patients who crossed over and did better on tavasomig, with the intention of trying to see again if you can tease out anything that's specific about this patient subset?
We collected archive biopsy specimens in the study, and we're now going to embark on sort of a comprehensive biomarker analysis. I think the real onus on us is to do as much work as we can to try to tease out why, you know, those patients who crossed over did so amazingly well. Yes, to your question, we collected biopsy specimens, and we're going to embark on a comprehensive, you know, biomarker analysis of those specimens and in addition, blood samples, of course.
Okay. To the extent that this potentially becomes a conversation with FDA about an accelerated approval pathway. Any additional or just initial thoughts right now as to where you would look to conduct a confirmatory phase III trial, whether that would be in the second line, or would you look to do this in the front line and just how quickly you think you might be able to get this up and running?
Sure. You know, just to repeat, it is our intention to seek full approval based on this study. You know, these data are only single-digit days old here for us. You know, just some high-level thoughts on your question. You know, adding tovecimig to the frontline regimen of gemcitabine, cisplatin, and durvalumab is something that we're doing right now. I don't want to go too far into a rabbit hole here with you, Steve, something else that we could do is we could swap our own PD-1/PD-L1 blocking antibody 8371 for durvalumab in that study, which would be something that we'd be incredibly excited to do.
Our frontline study adding tovecimig to gemcitabine durvalumab ongoing at MD Anderson, and we're, you know, continually reviewing data from that study with the investigators, you know, again, to help us think about future studies. Another study that we could think about would be tovecimig paclitaxel versus FOLFOX in the second-line study. You know, maybe that's a study that we do in Europe, where FOLFOX is probably used a little bit more commonly in the second-line setting than it is in the U.S.
Okay, that's helpful. Just lastly, I understand you're gonna have kind of a more comprehensive update of safety data at a future medical meeting, but is there just anything that you can say about DLL4 specific toxicity? I guess I'm specifically referring to something like pulmonary hypertension.
Sure. You know, You and I have talked about this before. It's as a bispecific antibody, it's hard to ascribe anything to either end of the molecule, right, either, you know, safety or efficacy. But since you asked specifically about pulmonary hypertension, you as you all review this slide deck, you'll see that on slide 13, pulmonary hypertension is not on that slide. In the study, there were three AEs of pulmonary hypertension, 2.8%. Something substantially lower than we saw in our phase I and phase II studies in Korea. I don't have an explanation for that. I do know that we looked much more thoroughly for that in this study with serial BNP measurements and serial echoes.
We saw it at an incidence of 2.8%.
Yeah. That's helpful. Thanks, Tom.
Thank you.
Our next question comes from the line of Michael Schmidt with Guggenheim Securities. Please proceed with your questions.
Hey, thanks for taking my questions. I'm still trying to wrap my head around the OS data, I suppose. I guess, Tom, any additional hypothesis why the crossover patients did so much better than patients who received tovecimig plus paclitaxel in the treatment arm? I'm just curious if there's anything maybe you can comment on post-progression treatment in the tovecimig treatment arm, where, you know, patients perhaps had less opportunity to receive third-line therapies than the crossover patients, for example. Also curious if you saw any imbalances in prior PD-1 use in the various treatment arms.
Okay, multiple different questions there. I'm gonna take those in reverse order. More than 90% of patients in the study had a prior PD-1 blocking regimen. The, you know, the vast majority of patients had either durvalumab or pembrolizumab. We don't have all of the post study therapy data analyzed so far. The one thing I did look at at the end of last week, only because it was so topical, I think there was only one patient in the study who got a BRAF inhibitor, so I don't think post progression therapies are an explanation for that. Again, you know, that's very preliminary.
Michael, the first part of your question is, of course, fascinating, you know, which is, you know, the first part of your question is why do we see this? One obvious hypothesis is maybe two, you know, two months, 1.9 months, you know, two cycles of paclitaxel, does that condition the tumor microenvironment to be more receptive to angiogenesis inhibition with tovecimig? You know, that's sort of a fairly straightforward hypothesis. I think we're thinking about that. You know, we're gonna do some preclinical work on that. That might be an interesting thing to test in maybe some other indications, as we move forward in the future, you know, now that we have this, you know, unequivocal, you know, demonstration of efficacy here.
As we think about moving into other indications, maybe that's a question we think about in gastric cancer, where paclitaxel is part of the standard of care, you know, maybe couple of cycles of pac and then add tovecimig into that, you know, obviously, you know, incredibly early days in our thinking about that observation.
Okay. Maybe just a follow-up, I'm just curious if you've had any additional regulatory interactions, with the FDA since the study started originally. I'm just wondering, you know, how you feel about approvability with the 1.05 hazard ratio in ITT.
Sure.
I mean, generally, I believe FDA is looking for an HR that's less than one in OS for these types of studies. Obviously in BTC, in cholangiocarcinoma, there's a lot of history of accelerated approvals.
Yep.
The drug clearly works on PFS and ORR, and I'm just curious if you've had any other interactions with the agency, throughout the trial.
No is the specific answer to your question. you know, but I think, you know, again, it's very, very important, I think, you know, to think about this hazard ratio. When you see a hazard ratio of 1.05, you know, the knee-jerk reaction is that, you know, somehow, you know, there's toxicity in the experimental arm. That's not the case here. You know, the reason that the hazard ratio is 1.05 is because the control arm patients who crossed over did so amazingly well. in terms of the very broad general question you asked, Michael, you know, there are a number of examples of approvals with either ORR or PFS where the hazard ratio on OS is above one.
I'm not, I'm not worried about that, especially because it's so clear that the patients who crossed over really drove the hazard ratio. I think, you know, because of that, you know, this analysis of the crossover patients, I think is a demonstration of efficacy of the drug.
Great. Thank you.
Our next questions are from the line of Li Watsek with Cantor Fitzgerald. Please proceed with your questions.
Hey, good morning, guys. Thanks for taking our questions. Maybe just a follow-up for crossover versus non-crossover patients, you know, just curious any, you know, difference in the subsequent treatments or other factors could have also contributed to the OS difference that you observed and what other crossover analysis that you guys may be able to conduct to show there is OS benefit to the FDA?
Sure. That's a fantastic question. In terms of the first half of your question, Li, I don't have all of that analysis done yet, but our, you know, very early review of that data suggests that it's not post-study therapy. The second part of your question is absolutely fascinating, you know, because as many of you know, you know, in the ClarIDHy study, which was ivosidenib versus placebo, the crossover adjustment RPSFT analysis was done post-hoc in that study. While the RPSFT was pre-specified here, the statistical assumptions were not met, but there are multiple other statistical methodologies that can be used to look at adjusting OS curves for crossover, and we're exploring those other methodologies now.
Thank you.
The next question is from the line of Charles Hsu with Life Sci Capital. Please proceed with your questions.
Hey, good morning. Thanks for providing these data and for taking our question. I believe these may have been somewhat addressed from different angles, how do you think the FDA might be looking at some of your OS data here, you know, in light of hitting ORR as well as PFS? Particularly since the FDA seems to place a bit of an emphasis on no detriment on overall survival relative to the hazard ratio that is at least numerically above one. Related to that somewhat, maybe just circling back to the RPSFT, what exactly was those certain statistical assumptions that were not met in this particular study?
You know, could you provide some color as to, you know, perhaps why it looks like when you ran that analysis, the OS hazard ratio seems to have gone up to 1.13. Thank you.
Okay. Very important questions. Let me take the second part first, which is a two-part question. When the ITT hazard ratio is above 1, the RPSFT cannot work. It's that simple. We're providing the RPSFT numbers here today solely for full disclosure. Those numbers are completely irrelevant because the assumptions for the statistical method were not met. Now, the first part of your question I want to just, you know, take head on, right, which is, you know, and specifically, you know, I'm going to use your word harm, right? Again, the assumption is with a hazard ratio of 1.05 that that's evidence of harm.
That is fundamentally not the case here, and that is the single most important take-home message of these data because the hazard ratio of 1.05 , I would strongly argue, is prima facie evidence of benefit because the crossover patients that did so well are the patients who drove the hazard ratio on the ITT analysis above one. Those patients that lived 12.8 months took the ITT hazard ratio above one because those patients were included in the control arm because of where they were randomized. So the ITT analysis is not evidence of harm. It's evidence that the crossover patients did incredibly well. This is a super important point.
Understood. Thanks for taking our questions.
Thanks, Charles.
Our next questions are from the line of Matt Phipps with William Blair. Please proceed with your questions.
Morning. Thanks for taking my question. Can you remind us, for patients who did cross over, what inclusion criteria needed to be met for them to be allowed to cross over? I guess, you know, were there patients who didn't cross over who wanted to but didn't meet any of that criteria? Then I guess just confirming, you have not yet done something like a two-stage adjustment or inverse probability of censoring as other sensitivity analysis around this crossover OS. Thank you.
Um, okay, the, uh, second part of your question, um, uh, very straightforward. No, uh, we have not, uh, done, um, we have not done a two-stage analysis, uh, on the crossover. There are a couple of other, uh, statistical analyses that we're doing o-on the crossover as well, um, that are in progress. In terms of the first part of your question, I went back to the schema. Uh, the main criterion for a crossover was a centrally confirmed progression event. Uh, so the patient was required to have a BICR confirmed progression event and then, um, meet some of the selection criteria, uh, for the study. Um, Matt, I'm sorry, this very specific question you asked, I don't know the answer to. Uh, how many patients wanted to cross over but didn't, um, for whatever reason, I'm sorry, I don't know the exact, uh, answer to that.
Uh, uh, I can look that up, um, as we, uh, can, you know, continue our evaluation of the data.
Okay. Thank you.
Our next question's from the line of Sean McCutcheon with Raymond James. Please proceed with your questions.
Hey, guys. Thanks for the question. Just one from us. Can you speak to the PFS results in the context of what would be expected for FOLFOX and second-line BTC? Obviously, you receive this question a lot.
Yep.
-given the median PFS below five, I think some context necessary for how you're thinking about the competitive profile relative to standard chemo, uh, in this setting. Thanks.
Sure. Sure. Um, so, uh, I just put up the PFS slide again, 4.7 months in the combination arm versus 2.6 months, uh, in the paclitaxel only arm. You know, I think the CHOI study, uh, which was a randomized trial of Full Fox versus Full Theory, uh, is the, um, you know, the best benchmark here for what to expect. 2.1 month median PFS for Full Theory, uh, 2.8 months median, um, PFS for Full Fox. You know, that's what people see, uh, with these chemotherapy with each of these three drug chemotherapy regimens out there. Um, you know, in ABC-06, which was Full Fox versus best supportive care, there was a very long scan frequency, um, uh, there. Um, and, um, more importantly, in ABC-06, the control arm was not scanned.
We don't know whether or not FOLFOX in ABC-06 was better than supportive care. Also, very importantly, our study is blinded independent central review, so all of our PFS data are BICR assessed progression. ABC-06 was all investigator-assessed. I don't think there's any KOL who believes that the PFS with FOLFOX is greater than three months.
The next question.
That's-
Is from the line of John Noon.
By the way, that's why. Sorry. That's why we use 3.0 months as the powering assumption for median PFS in the control arm in our power calculations. Sorry, John, go ahead.
Thanks a lot for taking my question. Um, just kinda going back a couple questions, I think as a follow-up on Buren's original question, do you have any sense as to the discontinuation rate for the combination arm versus the patients who crossed over from the control? I'm just curious if you've been able to look at that to tell whether or not, uh, perhaps for whatever reasonThat discontinuation rate was different either one way or the other.
Uh, we have not looked at that. I'm sorry. Um, you know, something that we'll be looking at, you know, in the coming weeks.
Okay. Thanks.
Next question is from the line of Ren Benjamin with Citizens. Please proceed with your questions.
Hey, good morning, guys. Thanks for taking the questions. Um, what was the... Can you just remind us, what was the study power to detect in terms of OS delta between the two arms? And if you, if you look at the OS of tavasomig treated patients, both crossover and the original treated patients versus those not, what are, what do those two numbers look like? And just, have you done any sensitivity analyses regarding prior therapies and how that might have impacted the PFS or OS? Thanks.
Okay. Um, uh, so a multi-part question there. Um, let's start with the power calculations. Uh, the original power calculations were for OS, were 6.2 months in the control arm, and that was based on, uh, a multiple different FOLFOX studies. Um, uh, both Choi and ABC-06, uh, had a median OS of 6.2 six months in the FOLFOX arm. The assumption on OS in the combination arm was 10.9 months. Uh, the pooled median there was right around, uh, nine months based on a two-to-one, uh, randomization. Um, so those were the power calculations. Okay. The second part of your question is, um, partly here.
Uh, the median OS in the paclitaxel only arm was 6.1 six months, very consistent with what you see with FOLFOX, and the median OS in the original, uh, combination arm patients was 8.9 eight months. Um, so that's probably the correct comparison, 8.9 versus 6.1 . Ballpark, you know, forty-ish percent improvement.
Got it. And then any other just subset, uh, analyses that you're, that you're, that you looked at regarding maybe prior therapies or anything else we should be looking at that might further support the OS benefits?
Uh, so, uh, no, um, uh, we have not done that specific, uh, analysis, uh, Ren. Um, um, uh, just as I mentioned earlier, um, you know, so many patients, greater than ninety percent, had Gemcitabine plus a checkpoint inhibitor. Um, you know, perhaps we could check durvalumab versus pembrolizumab, um, but we have not done that.
Thank you.
Our next question is from the line of Stephen Willey with Stifel. Please proceed with your questions.
My follow-up was unanswered. Thanks.
Thank you. The next question is from the line of Joe Pantginis with H.C. Wainwright. Please proceed with your questions.
Hey, good morning. This is, uh, Sarah on for Joe. I just wanted to kind of hone in a little deeper on the, uh, PFS numbers as you discuss, uh, potentially going or seeking accelerated approval. Looking at PFS is, um, are you thinking the numbers you, uh, got that you presented today represent an approvable now metric? And I'm just kinda curious how you're weighing that, um, against your data for OS and even the ORR, um, as well, maybe, um, as you look to move ahead with your FDA meeting. Thank you.
Sure. Um, you know, I think the most, uh, you know, in addition, obviously, you know, to the extraordinarily low P value, you know, the hazard ratio here of 0.44 is without any question an approvable number. That is a fifty-six percent reduction in the risk of progression.
Okay. Thank you. That's helpful.
Thank you. Our final question is from the line of Albert Lowe with Craig-Hallum. Please proceed with your questions.
Hi. Did the portion of patients that crossed over differ from your expectations, in the design of the trial? Did this aspect affect the feasibility of the RPSFT analysis?
That's an interesting question. It was very, very hard to estimate, you know, ahead of time, you know, the fraction of patients that would cross over. I think 54% is, you know, maybe a little higher, you know, than we had initially thought of. In addition, you know, I think something that was, you know, also affected, you know, the RP-SFT a little bit, you know, was the, you know, the timing of those crossovers. It's a very good question. You know, it's a very, very complicated question also.
You know, I think it's a maybe a little higher than we had originally thought when we were designing the study, because again, crossover patients would be treated in the third line setting, where, you know, the number of patients that make it out of a second line therapy into third line setting is, you know, that's not a huge number. So it's a little higher, I think. Good question. Tough to answer.
Yes. Thank you.
Thank you. At this time, this will conclude our question and answer session. I'd like to turn the floor back over to Dr. Thomas Schuetz for closing comments.
Great. Thanks so much. Just wanted to thank everyone for joining the call today. Really appreciate your time this morning. You know, I think I'll probably just close by, you know, sort of going back to the next steps slide. You know, we're super excited about the data we have. We have an unequivocal demonstration of efficacy multiple different ways here. We're going to put everything together, meet with the FDA to discuss these data in advance of a planned BLA submission. If that discussion goes well, we should then be in a position to initiate the BLA submission toward the end of this calendar year. Look forward then to BLA review and potential U.S. approval of tavasomig in 2027. Thanks again.
Thank you. This will conclude today's teleconference. Ladies and gentlemen, thank you for your participation. You may now disconnect your lines at this time, and have a wonderful day.