Greetings, welcome to the Sutro Biopharma webcast. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the presentation. If anyone on the phone should require operator assistance, simply click star zero on your telephone keypad. If you're connected on the webcast, for any technical support, click the question mark icon on the upper right corner of your screen. Please note this conference is being recorded. I will now turn the conference over to our host, Ed Albini, Chief Financial Officer. Thank you. You may begin.
Thank you, Operator. Good afternoon, everyone, and thank you for joining us. With me on the call are Bill Newell, Chief Executive Officer, Dr. Stan Frankel, an esteemed member of our Scientific Advisory Board, Dr. Trevor Hallam, President of Research and Chief Scientific Officer, and Jane Chung, Chief Commercial Officer. We also welcome on the line Dr. R. Wendel Naumann of the Levine Cancer Institute at Atrium Health. This afternoon, we issued a news release that you can find on our website at www.sutrobio.com, which includes an update from our phase I dose expansion study of STRO-002, also known as luveltamab tazevibulin or Luvelta, in ovarian cancer, as well as our plans moving forward in respects to a potential registrational study.
The agenda for today is as follows. Bill Newell will open up the discussion. Dr. Wendel Naumann will present the dose expansion data for Luvelta. Bill and Dr. Frankel will provide details around our planned phase II/III study and the registrational path forward. Bill and Jane Chung will give a brief overview of the market opportunity in ovarian cancer. Bill will then provide brief closing remarks. We will open up the Q&A portion of the call featuring Dr. Naumann along with the Sutro team here today.
Before we start, I would like to remind you that today's call will include forward-looking statements. These forward-looking statements are based on Sutro's expectations and assumptions as of the date of this call. Each of these forward-looking statements involve risks and uncertainties that could cause Sutro's clinical development programs, future results, or performance to differ significantly from those expressed or implied by the forward-looking statements.
Please refer to Sutro's filings with the SEC, including our 2021 Form 10-K, for information concerning factors that could cause Sutro's actual results to differ from those expressed or implied in the forward-looking statements discussed on this call. Except as required by law, Sutro assumes no obligation to update any forward-looking statements discussed on this call to reflect any change in expectations, even as new information becomes available. With that, I would now like to turn the call over to Bill Newell for a welcome and introduction.
Thank you, Ed, and thanks everyone for joining our call today. While there has been considerable progress in the treatment of many cancers, ovarian cancer remains an outlier. There is a significant need for newer and better therapies for patients with advanced progressive ovarian cancer, including platinum-resistant ovarian cancer. Today, we will be taking you through the most recent findings from our dose escalation phase I study of STRO-002 or luveltamab tazevibulin, which we've shortened to Luvelta, our novel folate-receptor alpha-targeted antibody drug conjugate. We will also discuss interim data from our newest exploratory cohort, which we call Cohort C, that explored the use of prophylactic pegfilgrastim when given in conjunction with the highest dose of Luvelta.
Based on these results and our conversation with U.S. FDA last year, we continue to believe that Luvelta has the potential to become an attractive new treatment option for patients with platinum-resistant ovarian cancer. Luvelta was precisely designed to target folate-receptor alpha, a molecular target highly expressed on ovarian and endometrial cancer cells. The target is also highly expressed in a rare pediatric acute myeloid leukemia known as the RAM phenotype. In case you missed it at ASH in December, we presented impressive findings from our compassionate use program involving young children with this extremely rare and aggressive form of AML.
For today, the focus is on ovarian cancer. As you may have already read in this afternoon's press release, our latest results strengthen the convictions we expressed when we presented our interim results a year ago. Luvelta has demonstrated clinically meaningful activity in platinum-resistant ovarian cancer patients who are folate- receptor alpha- selected, meaning their tumor proportion score or TPS is greater than 25%. As a reminder, TPS is the percentage of a patient's tumor cells staining positive for the target regardless of the intensity of that staining. Based on the data generated, we have selected tumor proportion score greater than 25% as the most appropriate scoring algorithm for identifying the target patient population for Luvelta.
Importantly, this folate-receptor alpha-selected patient population potentially comprises up to 80% of platinum-resistant ovarian cancer patients. Therefore, Luvelta has the potential to benefit the largest share of platinum-resistant ovarian cancer patients compared to other folate-receptor alpha-targeted therapies. The additional data and follow-up confirm our interim efficacy results. Folate -receptor alpha-selected patients who started at the higher dose of 2.5 mg/kg had an overall response rate or ORR of 43.8%. As a reminder, single-agent chemotherapy, which is standard of care for this patient population, has an ORR of approximately 10%.
This higher starting dose also showed clinically meaningful median duration of response of 5.4 months and a median progression-free survival of 6.6 months. Furthermore, irrespective of starting dose, patients experienced a 37.5% overall response rate, a median duration of response of 5.5 months, and median progression-free survival of 6.1 months. The third important confirmation of our results was that the safety profile has remained substantially unchanged from what was reported a year ago. The primary signal from the dose expansion cohort was predominantly asymptomatic transient neutropenia. Importantly, even though we do not treat patients prophylactically with corticosteroid eye drops, we are not seeing the sort of substantial ocular events that are seen with other folate- receptor alpha-targeted therapies or antibody drug conjugates targeting other antigens.
We used Cohort C as an exploratory study to better understand how we might maintain patients on the higher 5.2 mg/kg dose and ameliorate the risk of grade 3 or higher neutropenia. Fifteen patients with advanced ovarian cancer were enrolled. Our initial evaluation of the first 10 patients in this cohort, when compared to patients in dose expansion at the higher dose of 5.2 mg/kg without prophylactic pegfilgrastim, showed decreased rates of neutropenia and dose delays.
Specifically, the data demonstrated that rates of grade 3 or higher neutropenia in the first cycle were reduced by 85%, and dose delays in the second cycle were reduced by 66.7%. Discussions with FDA last year have provided us with important insights into their thinking regarding Project Optimus and their evolving views on accelerated approval. We took their comments to heart and have now settled on a protocol designed to support a BLA. In this single study, we maintain our opportunity for accelerated approval on the same timeline as we had previously expected and accelerate by approximately two years the full approval opportunity. We think this is the most efficient, cost-effective trial design for Luvelta that will provide regulatory authorities with the data package to support approval of Luvelta. We expect the registration-directed study to be initiated in the second quarter of 2023.
Moving on to the next slide. That advanced ovarian cancer needs newer and better therapies is undeniable. For patients with advanced disease, treatment options have been very limited until recently, and even the newest treatment option is only available to a minority of patients. As Dr. Naumann will attest, platinum-resistant ovarian cancer still represents a high unmet medical need. We designed Luvelta to be a next generation antibody drug conjugate using our proprietary cell-free protein synthesis technology. Our purpose was to create a therapy that could be more broadly effective than other folate- receptor alpha-targeting molecules with an improved therapeutic index.
Luvelta is the first of a new generation of homogeneous ADCs designed to be more efficient and precise at delivering payload to tumor cells to drive immunogenic cell death. We introduced novel specific positions in the antibody for high-fidelity attachment of our proprietary hemiacetal and payload-cleavable linker. Choosing the best combination of attachment positions ensures maximal impact with every antibody-tumor binding event. In this way, efficacy is improved over conventional technologies and apparent even in lower antigen-expressing tumors. This efficiency of delivery minimizes systemic exposure to free payload that we believe also minimizes the risk of serious tolerability issues such as ocular damage and pneumonitis.
Once the hemiacetal payload has been released from its cleavable linker in the target antigen-expressing tumor cells, it will then kill secondary surrounding tumor cells, this is known as a bystander effect, regardless of target antigen expression. Subsequently, the payload will wash out into the systemic circulation where it is quickly cleared, reducing risk of collateral damage to healthy tissues.
This slide details the enrollment of cohorts in our initial phase I study for patients with advanced ovarian cancer. As part of our dose escalation, we started to see efficacy at the 2.9 mg/kg dose and noted that the top doses of above 6 mg/kg were not as well tolerated. We initiated the dose expansion phase with Cohort A in January of 2019. Enrollment was in an unenriched patient population, and we required tissue samples in order to be able to determine an appropriate enrichment strategy. We enrolled 44 patients who were randomized between two intermediate doses from the dose escalation cohort, 5.2 mg/kg and 4.3 mg/kg.
As the following data will illustrate, we've now confirmed that a patient selection strategy using a tumor proportion score cutoff of above 25% is the most appropriate patient population for Luvelta. Thirty-five of 44 patients in Cohort A were determined to be in the folate- receptor alpha-selected group, and of those 35 patients, 32 were RECIST evaluable. As I previously mentioned, Cohort C enrolled 15 patients, and the protocol called for patients dosed at 5 mg/kg every three weeks to be treated with prophylactic pegfilgrastim, which was administered on day eight after each treatment of Luvelta. At the time of our data cutoff of December 8th, we had initial data on the first 10 patients.
The bottom part of this slide shows the patient demographic-graphics for Cohorts A and B, and as you can see, the patients were generally well balanced, and patients had similar degrees of prior treatment. Of note, the vast majority of patients had previously received bevacizumab and a PARP inhibitor.
I would now like to introduce Dr. Wendel Naumann. He is a co-principal investigator in the Luvelta dose expansion study and currently Professor and Director of Gynecologic Oncology Research and Associate Medical Director of Clinical Trials at the Levine Cancer Institute of Atrium Health. He serves as a board member of the Executive Council of the Society of Gynecologic Oncology and the Chair of the Education Committee and a Co-director of the SGO Winter Meeting. His clinical experience includes targeted therapies and immunotherapies, and he runs the phase I trials in gynecologic oncology of the Levine Cancer Institute. Dr. Naumann?
Thanks, Bill. I'm really excited about these data with Luvelta. This is great. You emphasize the unmet clinical need, and it's very frustrating as a physician to have a patient population where the response rate to conventional chemotherapy is 10% or less, and there are very few options. These patients survive only about 12 months. We really definitely need new treatments. As you mentioned, the expansion cohort of 44 patients, there were 41 of these that were valuable for response. When broken down by folate- receptor alpha expressions by IHC, nine patients had a TPS score of less than or equal to 25%. If these patients are excluded, the overall confirmed response rate, regardless of starting dose in the remaining 32 patients enriched for folate expression was 37.5%.
In the next set of figures, the response rate is broken down by the TPS score. Those patients with a TPS score of 25% or less had a confirmed response rate of 11%. In those patients with a TPS score between 25% and 75%, the confirmed response rate was 33%. For those patients with a TPS score of greater than 75%, confirmed response rate was 40%. For patients with a TPS of less than 25%, the duration of response was short at 2.9 months, compared to 5.6 and 5.5 months for the higher expressing cohorts. The last set of figures shows the response rate by starting dose of Luvelta.
The 16 patients in the folate- receptor alpha-selected population got a 4.3 mg/kg dose at a confirmed response rate of 31%, compared to the 16 patients starting at the 5.2 mg/kg dose, but a confirmed response rate of 44%. The duration of response data demonstrated clinically meaningful durability regardless of the starting dose, and the PFS data show important patient benefit even for those who did not reach partial RECIST response for folate-receptor alpha-selected population. It is important to note the TPS scoring in this trial represents any amount of folate- receptor alpha expression, not just limited to those with 2+ expression or greater.
Next slide, please. This is a waterfall plot for the patients who had a TPS score greater than 25%. This represents the folate-receptor alpha-selected patients. Twenty-two of the 32 patients or approximately 69%, had some benefit from treatment with respect to tumor shrinkage. As an oncologist and as a patient, this is clinically meaningful, as it means you remain on treatment even though you may not have met the criteria for RECIST-defined partial response. The unconfirmed response rate was 44%, and the confirmed response rate was 37.5% in the folate-enriched group. It's interesting to note the patients who started the 5.2 mg/kg dose had a response rate of 44% versus 31% for those starting at the 4.3 mg/kg dose.
In the chart on the bottom right, you can see that the response rate was higher in the 5.2 mg dose, despite the fact that the 4.3 mg dose cohort had a somewhat higher rate of TPS greater than 75%. That's 56% versus 69%. Please note the folate alpha expression at the bottom of the waterfall plot. Many of the confirmed responses were in patients with a TPS score of less than 75%, as denoted by the yellow boxes. The overall disease control rate was 80% in this FR alpha selected group, regardless of starting dose. Given the lack of other options for these patients, this is very clinically significant.
Next slide, please. This is a spider plot color-coded based on the dose cohort. The 5.2 mg/kg cohort is dark blue, and the 4.3 mg/kg cohort is light blue. The response rate appeared to be deeper and more rapid in the 5.2 mg/kg dose cohort. Patients who achieved a response often had a durable response, and several of these patients remained on treatment greater than one year. Next slide, please. This is a swimmer's plot of the folate-receptor alpha-selected group, broken down by starting dose. Of note, 50% of the responses persisted beyond the 24-week landmark, as indicated by the dotted vertical line in both the 5.2 mg/kg dose cohort and the 4.3 mg/kg dose cohort. Those reductions are noted by the lighter blue and gray bars.
In the 5.2 mg group, those reductions were common, but the duration of response continued after the dose reduction. Also, many of the patients who are on the study greater than 24 weeks did not have a high folate-receptor alpha expression, as noted by the light yellow boxes to the left of each lane. This demonstrates clinical benefit in patients who would not be eligible to receive other folate-receptor-targeted therapy that are labeled only for higher levels of folate-receptor alpha expression. I would like to point out that there were six patients in this trial that stayed on for greater than 24 weeks that either did not meet the definition of partial response or had a partial response that was not confirmed but did have prolonged stable disease and clinical benefit.
The dose intensity of the 5.2 mg/kg dose was 20% greater than the 4.3 mg/kg cohort, but likely would have been higher as the dose intensity was reduced due to delays secondary to neutropenia. Next slide, please. To address the issue of neutropenia, Cohort C looked at the addition of growth factors to the regimen. Due to the half-life of the drug and the timing of the neutropenia, the G-CSF was given on day eight. Prophylactic G-CSF reduced the incidence of grade 3 or higher neutropenia at cycle one from 67% down to 10% and decreased dose delays from 76% to 30%.
Next slide, please. Overall, Luvelta was well tolerated. The most frequent treatment-emergent adverse events greater than grade 2 in two or more patients are shown in this table. Neutropenia is the most common toxicity, with grade three or greater neutropenia in 65% of patients mg/kg and 76% of patients in the 5.2 mg/kg dose cohorts. In the majority of patients, this neutropenia was uncomplicated. Arthralgias were the second most common toxicity. 26% of the patients had grade three in the 4.3 mg/kg cohort and 10% in the 5.2 mg/kg cohort. Of note, all these patients are pretreated with paclitaxel and were likely to have some baseline neuropathy, which would make their arthralgias worse. Of significant interest, there was rare grade three or greater ocular toxicity and no greater than grade 3 pneumonitis that's been associated with other ADCs.
There were several grade three events that were felt to be unrelated to study drug, including large and small bowel obstructions due to the progression of metastatic disease and acute kidney injury that was attributed to other factors, including sepsis and dehydration. There were also two pulmonary emboli that were felt to be unrelated to the study drug. Overall, Luvelta had an excellent efficacy in patients with platinum-resistant ovarian cancer who had a TPS score folate-receptor alpha of greater than 25%. Luvelta was well-tolerated and not associated with high frequencies of clinically relevant toxicities seen in other antibody drug conjugates that have been used in patients with ovarian cancer. I'm going to turn this back over to Bill for an overview of the registration pathway for Luvelta. Thanks.
Thank you, Dr. Naumann. Based on these results, we're ready to move into our registration-enabling study. We believe our target product profile is strong with the potential to treat approximately 80% of platinum-resistant ovarian cancer patients with equal or better efficacy than the recently approved folate- receptor alpha-targeting therapy and with a more tolerable safety profile, particularly for the higher dose in light of the addition of prophylactic pegfilgrastim. I would now like to ask our SAB member, Dr. Stan Frankel, to go through the integrated phase II/III study design. Stan?
We are excited to initiate the registration-directed study, REFRaME, in women with relapsed refractory ovarian cancer who would otherwise receive single-agent chemotherapy as current standard of care. We have chosen to proceed with a multi-part, integrated, seamless phase II/III trial design to generate a robust clinical data set that will allow for the potential for accelerated approval while also providing the basis for consideration of a regular approval. We've had helpful discussions with the FDA on Project Optimus and the evolving FDA positions on accelerated approval that have informed our decision. Patients enrolled will be folate- receptor alpha- selected, meaning their TPS score will be greater than 25%, and they will be platinum-resistant, having received one to three prior lines of therapy, including bevacizumab.
In order to provide additional data on dose optimization, the phase II portion of the study will begin with a randomized run-in dose confirmation phase, where we will evaluate 25 patients treated with Luvelta 5.2 mg/kg, with pegfilgrastim delivered prophylactically at day eight of cycles one and two, and then a step-down to dose Luvelta at 4.3 mg/kg. The second arm will enroll 25 patients treated with Luvelta at 4.3 mg/kg without prophylactic pegfilgrastim. Following this run-in phase, additional patients will be randomized between three treatment arms. The same two Luvelta dose regimens evaluated in the phase II dose optimization run-in, and a third standard of care chemotherapy arm. Agreement with FDA on the optimal Luvelta dose, the non-optimal dose of Luvelta will be dropped, and the trial will complete its planned approval.
During the conduct of the randomized phase III portion of the study, when response data and durability data are available for approximately 110 patients at the optimal Luvelta dose, Sutro will assess the overall response rate of the subgroup to support submission of a BLA for accelerated approval. When approval of the phase III portion of the trial is complete, full approval can be sought based on progression-free survival as the primary endpoint. REFRaME is expected to begin in the second quarter of this year. Back to you, Bill.
Thank you, Stan. In parallel with our phase II/III study, we will continue to invest in Luvelta more broadly, including in endometrial and non-gynecologic cancers. As I mentioned briefly before, we recently reported positive data with Luvelta in pediatric AML at ASH in December, demonstrating the potential to extend benefit of our novel antibody drug conjugate to other patient populations who have a dearth of treatment options. We plan to meet with FDA soon to discuss the clinical path forward in this rare RAM phenotype pediatric disease patient population. As evidenced by a continuously growing data package, we're encouraged about Luvelta's ability to reach a broad array of patients and the commercial opportunity ahead. To that end, I would like to welcome Jane Chung, our Chief Commercial Officer, to provide a brief overview of the market opportunity, primarily in ovarian cancer.
Thanks, Bill. We've shared a lot of data with you today, and for commercial, it's important we have a simple story for Luvelta. To that end, I wanna make three simple points that will shape Luvelta's market potential. First is efficacy. Luvelta's efficacy is driven not by a small group of super high folate- receptor alpha expressers, but instead by a much broader patient population that includes folate- receptor low, medium, and high expressers with TPS greater than 25%, all of whom contribute to 80% of patients benefiting from this drug. Second is safety. With the initial look at Cohort C data, we see that Luvelta's safety is well managed with G-CSF, reducing grade 3 neutropenia down to 10%, and we're still not observing any clinically notable ocular and lung toxicity seen with other ADCs.
Third, testing. With Luvelta, folate-receptor alpha testing is simplified with TPS or tumor proportion score scoring only, without the need for intensity staining for PS 2+ and 3+, et cetera. What is the market potential for Luvelta? This favorable product profile we just discussed with you gives Luvelta multiple shots on goal to drive significant commercial opportunity in gynecologic cancers and beyond. In ovarian cancer, we just discussed the registrational plan for Luvelta that would benefit around 4,000 platinum-resistant patients as monotherapy. We are also studying Luvelta in combination with bevacizumab that would benefit an additional 2,000-3,000 patients in an early line maintenance setting. We also have an ongoing endometrial trial evaluating Luvelta across folate- receptor alpha expression levels.
For the beyond, we have a rather unique and large compassionate use program in a super rare pediatric RAM AML, where we've already treated over 17 patients and have shared positive clinical data at ASH. For which Luvelta has received orphan drug designation and a rare pediatric disease designation. Importantly, while this may not be a big commercial opportunity, it may accelerate our timeline to market and accelerate our readiness for ovarian cancer. In addition, we have some important translational work to do in lung cancer to define the strategies for folate- receptor alpha stratification. All of these opportunities make Luvelta a pipeline and a drug, and we are excited about the great potential.
Next slide. Where does Luvelta fit in the overall treatment paradigm in ovarian cancer? As mentioned already, platinum-resistant ovarian cancer remains a very high unmet need. In the current treatment algorithm, illustrated here, stage II to IV ovarian cancer women receive platinum-based chemotherapy, double chemotherapy, plus or minus bevacizumab following surgery. These women unfortunately receive lots of chemotherapy, and once they progress on a platinum-based therapy, within three to six months, they become platinum-resistant, where treatment options become even more limited.
Now, bevacizumab and PARP inhibitors are important treatment options if they provide more benefit in an earlier line and in maintenance. T he recent withdrawal of some of the PARP inhibitors from later lines actually leaves fewer options for platinum-resistant disease. Recently, mirvetuximab or Elahere received accelerated approval, yet their label restricts their use to 30%-35% of patients with folate- receptor alpha PS 2+ and 75% or greater positive staining, as represented by the dark golden circle on the right.
Despite the approval, there's still a high unmet need for the remaining 70% of platinum-resistant patients who are either ineligible for or unresponsive to Elahere. That is why we are super excited to see Luvelta bring meaningful benefit to a broader group of patients, upwards of 80% of patients who have folate-receptor alpha TPS greater than 25%, as represented by the much larger, yellow circle on the right. The visual on the right is simply to show that the mirvetuximab eligibility is a smaller subset of the larger Luvelta opportunity. Okay, I will turn it back to Bill.
Thanks, Jane. As you've heard today, this is an exciting time for Sutro as we prepare for our first pivotal study in an indication in which we believe we can offer a differentiated approach to treating patients who have exhausted their options. As we set out to do when at the onset of the dose expansion study, we've identified an enriched patient population for treatment with Luvelta using a TPS scoring algorithm of greater than 25%, which gives us a potential market opportunity of approximately 80% of platinum-resistant ovarian cancer patients. We've seen strong evidence of efficacy regardless of dose level, which is as good or better than recently approved folate- receptor alpha-targeted therapy. The higher starting dose looks even more beneficial in terms of response rates and PFS.
We successfully piloted a cohort that gives us confidence that we can ameliorate the high rates of neutropenia seen in patients who are dosed at the higher dose level by a short course of pegfilgrastim prophylaxis. No new toxicities have emerged, the safety profile does not show the significant ocular toxicities associated with other folate-receptor alpha-targeted therapies, even without the use of prophylactic ophthalmic corticosteroid drops. Finally, we have a path forward for accelerated approval that is efficient, is most cost-effective, and is designed in harmony with our data to maximize our probability of success. Our phase II/III clinical design was informed by our FDA discussion, the advice of our clinical advisors and regulatory experts, and the additional clinical data that we now have in hand.
We look forward to providing future updates on our development plans for Luvelta and to taking your questions in just a moment. On behalf of the entire Sutro team, I would like to thank all of the women who participated in our ovarian cancer studies, as well as their families, and the investigators and their teams who have devoted their lives to treating these women. We are so grateful for your help, as none of this would have been possible without you. With that, operator, you may open up the lines for our question-and-answer period.
Thank you. At this time, we will conduct our question-and-answer session. If you would like to submit a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would 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. Our first question comes from Roger Song with Jefferies. Please go ahead.
Great. Congrats for the impressive data. A couple of questions from us. The first one, just to help us to interpret the consistently longer PFS than the DOR. What is the potential driver for the longer PFS than the DOR? How clinically meaningful the data is appreciating this is a single-arm clinical trial?
Thanks, Roger. You know, we have a lot of stable disease that we're seeing in patients, and that really is what is driving the higher degree of progression-free survival. This is, you know, as we talked about during the slides that were presented, this is something that we think is what we were trying to achieve with this molecule, which is disease control, not only for patients who respond, but for women who do not respond. We're really pleased to see the progression-free survival numbers at this early stage. Of course, you know, we've been piloting the right treatment strategy for these doses, and I think Cohort C gives us confidence to move forward with a dose level that we believe could have even better benefit in terms of duration of response and ultimately progression-free survival in future studies.
Got it. Yeah, that makes sense. And also just a question related to the Cohort C. The safety profile, particularly for the neutropenia, it's very impressive, kind of very improved. Would you report efficacy data from that cohort knowing you will do the running phase for the dose confirmation in your pivotal. What is your kind of statistical assumption for the delta of DOR or ORR, DOR compared to the without the G-CSF?
Let me just really answer the question in this fashion. We wanted to understand whether prophylactic pegfilgrastim could significantly reduce the amount of grade 3 or grade 4 neutropenia. This initial look at the data, which is really relatively mature but important, suggested that right at the outset, we're able to ameliorate the risk of that and that we're able to actually keep patients on treatment with much fewer dose delays at cycle two. Obviously, we have a 15-patient cohort here that is going to be treated and going to hopefully have good duration of response to the extent they respond and good progression-free survival. It is way too early to have any data on that at that level.
You know, as we move forward this year and as we get that data, we'll look to talk about it in the future. Really, the cohort was designed to answer the question about ameliorating high-risk neutropenia.
Got it. Okay. Maybe just last one from us. For the pivotal study design, you have the control arm as the standard of care, we know more mirvetuximab, they will have the confirmatory study reading out this year and the potentially for the full approval. If the mirvetuximab is approved, will that be part of the standard of care in the control arm or your control arm basically is the chemo?
Yeah. We're looking at standard of care as being chemotherapy in this patient population. That's certainly been something that's been discussed.
Great. Thank you. Appreciate all the comments. Thank you.
Thank you, Roger.
Thank you. Our next question comes from James Shin with Wells Fargo. Please state your question.
Hey, thanks for taking my question again, congrats, guys. Roger dug into the DOR and PFS question, could you remind us how much of this phase I population for STRO-002 is going to be reflective of the phase II design? Could you remind us how much of this STRO-002 data had bevacizumab exposure?
Sure. In terms of bevacizumab exposure, it was approximately 70% in the folate-receptor alpha selected patient population. Given the sample sizes, we really didn't see any differences that were meaningful between patients who were bev- naive and bev- treated. With respect to the patient population, you know, we did not use prophylactic pegfilgrastim in this study, so really, Cohort C is a bit closer to what we're going to be seeing in one arm of the study that we're gonna do, this II/III study. The 4.3 mg/kg dose is exactly as we've been studying it in this Cohort A patient population. That's the closest thing that I can say.
The starting doses are really intended to give us additional data to satisfy Project Optimus, but we're optimistic that the 5.2 mg/kg dose with pegfilgrastim will prove to be the right dose for this patient population.
Appreciate it. One more, if I may.
Mm-hmm.
Going to the DOR and PFS, could I ask Dr. Naumann or Bill yourself, which is the better metric in this population? It sounds like PFS is and DCR is still valuable in this setting. Is that kind of the way to think about things?
I'll let Dr. Naumann answer this, and then I'll be happy to provide perhaps a supplemental comment if appropriate.
Yeah. Well, y ou know, I think the problem comes down to the fact that if you look at how drugs are actually used in clinical practice, versus our sort of the way we do research, we don't look at RECIST- defined responses in the progression is, y ou know, I'm more worried about the patient progressing clinically. I think you get a little bit of an artificial setup here, but , you know, it has to level the playing field. This is how we have to evaluate drugs. You know, for me, it's clinically important for patients to have prolonged stability of their disease. Again, that's, I think, probably the best way I can say it. Bill, I don't know if you have better.
No, I appreciate, Dr. Naumann, you're providing, kind of, the practical, practitioner perspective. I think obviously from a regulatory perspective, for accelerated approval, we are gonna need good response rates with good duration of response. Clearly for full approval, we're gonna need progression-free survival. You know, in this study, we're gonna get both of those answers on our pathway to getting this drug approved.
Thanks, James.
I appreciate it, Bill and Dr. Naumann. Thank you so much.
Our next question comes from Boris Peaker with Cowen. Please state your question.
Great. Thanks for taking my questions. First, I just wanted to clarify. In the REFRaME study, did the FDA know how far the randomized part of the study need to be enrolled for you to file on a single-arm part?
Sorry, can you repeat that question, Boris?
Yeah. How many patients do you need to have enrolled in the randomized part of the study in order to be able to file on the single-arm part of the study? Because we've heard comments from the FDA these days that, they want the confirmatory studies largely enrolled before filing on a single-arm trial for accelerated approvals.
Yeah, Boris, I'm gonna ask Stan Frankel to respond. Thanks, Stan.
Boris, we understand the FDA's position to be that the confirmatory trial needs to be substantially enrolled at the time of the action date. We would project that the study accrual at the time that they would actually be ready to grant the approval should be completed.
Got it. Do you have a sense of how long that would take?
You know, we have a number of centers that we're anticipating opening. This is going to be a global trial. Really until we get centers opened and start to see accrual rates, I'm not gonna be in a position to guide as to any definitive dates at this point in time. Y ou know, You'll have to stay tuned for that update, you know, at a future point.
Got it. Just last question. In your control arm, where you have the standard of care, would Elahere be allowed as part of the standard of care for patients that are eligible for it?
No.
Got it. Okay. Thank you very much for taking my question.
Thank you, Boris.
Our next question comes from Reni Benjamin with JMP Securities. Please state your question.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the update. Maybe just starting off, in the cohort three, you know, patients, ones with prophylactic G-CSF. Y ou talked about the lessening of dose reductions. In the pivotal study, you know, you seem to have an automatic sort of dose reduction, I guess, after you started at 5.2, you know, milligrams. Can you talk a little bit, unless I misheard it, a little bit about the rationale for why that's happening in that cohort?
Yeah, Reni, thanks for your question. You know, what we think the data is telling us is milligrams per kilogram induces the most rapid response. You can see from the data here that it's almost, you know, twice as long to get to that response at 4.3 mg/ kg. It happens usually very rapidly after the first few cycles. If you step down to 4.3, we know that that's sufficient to maintain the response and should have a better tolerability profile for patients. The theory was to keep patients at the higher dose level to induce a more rapid response using prophylactic pegfilgrastim, then step them down to a dose that can continue that response, and provide a more tolerable patient experience.
Did you guys evaluate any patients, you know, let's say, at 5.3 without the step-down, but keeping them on pegfilgrastim?
The study design allows patients in Cohort C to continue at 5.2 mg/kg with pegfilgrastim until there is a decision made to dose reduce them. There is not a required step down in Cohort C.
Got it. Okay. I mean, maybe I missed it in the slides, but did all the patients ultimately wind up getting a step down, or are there still patients that, you know, that continued at, you know, the higher dose all the way through?
Yeah. Cohort C is still ongoing. This is very early data. We're not in a position to talk more about what we're seeing other than that we are able to significantly reduce grade 3 or higher neutropenia at cycle one and to preclude to a much greater extent dose delays at cycle two.
Got it. Okay. Maybe a quick one for Dr. Naumann. You know, Elahere is approved. When we think about, you know, the different circles, right, that we're talking about in terms of a commercial opportunity, I mean, clearly , you know, there are those that are quite, it's easy enough for us to say, o kay, well, this is all, you know, I should say, Luvelta's opportunity. Within the, call it 30%-40% of patients that mirvetuximab would be used, you know, what would be the unmet need, I guess that as a clinician you would see when you have mirvetuximab approved for that group of patients? About, I don't know, how would you go about deciding which ones might get mirvetuximab, versus, you know, something like Luvelta?
First of all, I think the response rate is better with Luvelta. I think more importantly, you don't have the eye toxicity. I mean, it's it's pretty much a difficult quality of life issue if you can't see to drive or watch TV or do anything because your vision's blurry. That's a common toxicity with mirvetuximab. We don't see that with Luvelta. I don't have any problem putting patients on a clinical trial, you know, where we do standard of care versus Luvelta because you may get a better drug. Now, you know, I think most people would say once they progress on standard chemotherapy, if they were candidates for mirvetuximab, then you can cross over.
I don't think it's a detriment to the patient, but you're gonna have a lot more patients who qualify for Luvelta than for mirvetuximab.
Thank you, Dr. Naumann.
Reni, thank you very much for your questions.
Our next question comes from Asthika Goonewardene with Truist Securities. Please state your question.
Hi, guys. Thanks for taking my questions, and congrats on the data. I basically wanna ask Dr. Naumann, in his experience in treating patients in Cohort C, what has his experience been with the efficacy and the response rates? I've got a couple of questions for you, Bill, and the team.
I'll ask Dr. Naumann really to restrict his comments. We're really not getting into efficacy in Cohort C at this point in time. The data is way too immature for us to talk about that, Asthika. Thanks for asking.
Yeah. I haven't seen the data, so it's impossible from a treatment standpoint of individual patients.
All right. That understandable. I had to ask. Bill, maybe to you. When are we gonna see the next set of data here? I'm interested to know, when are we gonna see this data that we have here for Luvelta to be presented at a medical meeting? For the phase II/III, when do you hope to get part one recruited and versus the first data from that part one?
Okay, there's a lot of questions there. We're still looking at which medical conference we wanna present the data that we're talking about here. It will be at some point this year. Sorry. you know, We're not yet in a position to be able to guide to how long it will take us to go through that first part of our phase two-three trial. I will note that when we did our enrollment for cohort A in the dose expansion phase, we had 44 patients, and we had them all enrolled in about 11 months.
Beyond that, you know, we'll be looking to be aggressive in our enrollment, but I'm not in a position to guide to that, and certainly not in a position to talk about when we'll be able to put that data out in the public arena at this point.
Got you. All right, guys. That's all my questions I had. Thank you.
Thank you so much.
Our next question comes from Zhi Shu with Berenberg. Please state your question.
Great. Thank you very much, and congrats on data as well. My first question is around the alpha in your phase II/III trial. Can you comment on how much of the alpha is put on the ORR and the how much of it will be on the rest?
Hi, Zhi. Thanks so much for your question. It's a little broken up, but I think you were asking about us to quantify the hit to alpha. We've got a statistical plan. FDA had also indicated the same sort of notion that there is a minimal hit to alpha by looking at ORR for purposes of accelerated approval. We're not gonna quantitate it, but it is minimal.
Got it. Thanks very much. The second question I have is, you know, the potential for approval of Elahere, before you finish the phase III trial. Are you concerned with potentially you enroll patients with folate-receptor alpha expression level on the lower end of your target population so that you may see a downgrade of your response or efficacy metric at all? Thank you.
Thanks, Zhi. You know, we do plan a global clinical strategy. To your point, mirvetuximab would only be approved if it is fully approved in the United States. I think by pursuing that global registration strategy and making certain that we've got appropriate patient stratification, we should get the right level of patients at various expression levels, in order to give us a true benefit, understanding of our drug in this phase II/III study.
Got it. Okay, great. Thank you very much.
Thank you.
Thank you. There are no further questions at this time. I'll hand the floor back to Bill Newell for closing remarks. Thank you.
Thank you, Operator. I wanna thank everybody for listening in today. We will be looking forward to updating you as our data continues to mature and as we move our trial forward. Thank you again.
Thanks. This concludes today's conference. All parties may disconnect. Have a great evening.