You, everyone, join us for the 19th Annual Global Meeting of the International Gynecologic Cancer Society. Moving to early meeting allows IGCS to globally connect more frequently. It also provides IGCS members and attendees additional opportunities to share research, collaborate, and receive education from an international faculty of world-class experts in gynecologic cancer. While we are sad not to be in Rome this year, but we will next year for an in-person meeting, this year we have an outstanding program to share with you. Many dedicated individuals played a part in planning this conference, and I'm incredibly thankful for the hard work, especially this year's scientific program co-chair, Tom Herzog and Rena Kimi, to the entire 2020 program committee and the IGCS staff for their tireless work and ability to shift gears so quickly to fully digital meeting. Thank you, Roberto. Do you remember when we taped the promotional video for Rome while at IGCS last year in Rio? One of the things that I said on that video almost a year ago is, it's Rome, what could go wrong? We had no idea what was in store for us this year, do we? On behalf of myself and Rena Kimi and the scientific program committee, we are proud of the meeting we have planned for you on this exciting and interactive platform and grateful to so many people who switched gears from an in-person meeting to a hybrid meeting and ultimately to this ex-digital technology platform. When the IGCS council made the decision to postpone Rome until 2021, we were disappointed, but we knew this to be the best decision. COVID has changed our lives in many ways, including educational events and gathering with our colleagues. We feel strongly this ex-digital technology will allow us to participate, interact, and connect with each other in ways not seen in other virtual meetings. As Roberto mentioned, a big thank you to the 2020 program committee. You were all so willing to help with the planning of this meeting, grading abstracts, and executing this amazing event. We rely so much on course directors and moderators. Thank you for your commitment to the subspecialty and giving so freely of your time. Finally, a huge thanks to those working so hard behind the scenes, the entire IGCS staff, special call out to our executive director, Mary Aiken, the iCrossing team, Blue Events in Italy for their hard work in this transition. I'd be remiss in not thanking our industry partners for your commitment to IGCS and our educational missions. Truly a team effort it has been. Rainer? Yes, indeed, Tom. A real team effort. Welcome friends of all around the world to Rome, where I joined Roberto Angeli, our president, for this unique and very first digital congress of our society. Consistent with all IGCS meetings, IGCS 2020 will provide you with the opportunity to learn about the latest clinical advances as well as international developments in research, practice, and treatment for the care of women affected by gynecological cancer. Concurrent educational programming will run on four channels throughout each day to ensure that our delegates in all parts of the world are able to participate in the program. Many of the live sessions will have opportunities for audience participation through Q&A segments and polling. In addition to the scheduled programming, we are thrilled to offer 24 hours access to the meeting portal where delegates can access the digital exhibition hall for the latest updates and technology from our industry partners, very important. The surgical film cinema, which contains 21 films the abstract poster hall with over 300 posters and nearly 50 audio files where the poster authors further explain their research. Finally, it would be not a true congress if we didn't include a cultural event. We are grateful for the support from the ANIA Foundation to allow us to share with you a beautiful musical performance that we are calling the Women for Women Concert on Friday, September 11th at 7 p.m. Central European time. This will be a great way for us to celebrate women and hear the music of renowned European performers. We understand that a digital meeting comes with some challenges. If you experience technical difficulty while in the portal, please access the 24 hour chat feature found in the portal called IGCS link. If you cannot access the portal chat, please email the technical team at help at IGCSmeeting.com. The meeting portal will remain open 10 days after the meeting until September 24th, giving delegates the opportunity to watch recordings of the educational sessions and to access all the other features mentioned above. Robert. On behalf of the IGCS Council and the entire members, thank you again, Tom and Rainer. Your work here has been just incredible. The program is outstanding in so many ways and the society is indebted to you both. It is important for the gynecologic oncology community to utilize virtual solutions to share research experiences and ideas and get inspiration for the sake of caring for patients with gynecologic malignancies in this time. It is now time for our annual award ceremony. It is so very important to IGCS that we acknowledge individuals making exceptional differences in gynecologic oncology. Please refer to the program book or IGCS website to read more about each recipient and why they were chosen. The awardees recorded acceptance speeches which we will play now. The first is Mrs. Monica Bacon receiving the Lifetime Achievement Awards. Thank you, IGCS. This journey began for me in Montreal as a young nurse and feminist in the 1970s when David Popkin mentored me as his gynecology nurse. I only wish he was still with us to witness the fruits of his labor. Years later, I joined the world of gynecancer clinical trials at the NCIC Clinical Trials Group, coordinating the first international randomized phase three research study of Taxol for ovarian cancer. Not only was the treatment with Taxol successful, so was the collaboration. Canada, Scotland, Scandinavia, and the EORTC continued to partner together as the Ovarian Cancer Network. In order to additionally encompass endometrial and cervix cancers, rare tumors, translational research, and harmonization of operations and statistics, this network expanded to formally become the Gynecologic Cancer Intergroup in 1997. I would like to take a moment to thank and pay tribute to some colleagues who invested a great deal of their own personal time and efforts, which established the solid foundation of the GCIG. More and more national research groups joined the GCIG until it numbers more than 30 today. As well as international clinical trials, our GCIG successes include ovarian cancer consensus conferences, brainstorming symposia, educational workshops, and harmonized tools and templates. Our GCIG members established an international section in several editions of the Clinical Trials Manual published by the Oncology Nursing Society. Founded by Henry Kitchener, our GCIG's Cervix Cancer Research Network has provided invaluable outreach to emerging countries where cancer of the cervix remains too common a deadly disease. Over these many years, GCIG and IGCS have grown side by side as sisters. Amongst our many partnerships, my favorite and most gratifying has been our joint symposia for survivors and their caregivers. Retiring last year and stepping away from GCIG was one of the most difficult moves of my life. However, I continue to exercise my passion through advocacy and volunteerism. The Gynecologic Cancer Intergroup has not only provided me with professional fulfillment, but has been a source of some long-lasting and loyal friendships. To you, I send my thanks for your salutations on the occasion of this award. I am extremely fortunate that most of my career spanned an era when job performance was still at least as valued as credentials. It was also an era when choosing to be without a partner or children allowed me the energy and freedom to passionately pursue my career. I am truly, deeply honored to receive this award. My heartfelt gratitude goes out to all of you for this recognition. Thank you. I must say that I am humbled, honored, and at the same time excited to receive the Lifetime Achievement Award from IGCS. I was at the first IGCS meeting in Amsterdam back in 1987. And since then, I've never missed one single meeting of this society. So my professional career, which was almost entirely dedicated to the care of women with gynecological cancer, has grown in parallel with the outstanding progress of our society. So I have to thank all people who were instrumental to my achievements during the 40 years of my career now. My mentors, my colleagues, which are also my friends, my scientific partners, and above all, my patients, who were my most important partners during this wonderful profession. I'm glad to be part of this society. I'm glad to have served as a council member in the past and extremely grateful for this important recognition, which will give me further motivation to continue on my commitment to improve life of women with gynecological cancer through science, research, education, and compassionate clinical care. Thank you from the deepest of my heart. Thank you so very much for this wonderful recognition. The IGCS 2020 Excellence in Teaching Award means so much more coming from such an experienced group of educators. The best ideas are often the simplest, and the concept to expand the work of IGCS to global fellowship training was such a natural extension of IGCS' mission. I realize that the credit goes to those important leaders who supported this initial process, Michael Quinn, Mary Eichen, Kathleen Schmeller, Tom Randall, Linus Chung, Carolyn Johnston, Yinsun Yao-Joseph, Ted Tremble, and so many more. And of course, our sister organization, German Society of GYN Oncology, who was led by Dr. Eva Kandelhardt and Professor Kuhn Thorsten. On behalf of the Ethiopia IGCS fellows, I would like to thank the faculty who continue to support us every day, Dr. Robert Angioli, and many of our faculty who attend Ethiopian ECHO sessions, Michael Pearl, Anuja Gingren, Ritu Selini, Ellen Baker, Gustavo Foci, Elmer Huffman, Sven Becker, and our local team, who are really excellent, led by Dr. Dawit Desaling, Dawit Worku, Thaddeus Mekonnen-Azres, Dr. Tadessa Urgi, and Bethel Derje. And of course, our program officer, Susan Ralph. From the perspective of those of us on the ground, the IGCS Global Fellowship Program is making a difference today, and I have no doubt will continue to do so. In partnership with the Ministry of Health, we are working on expanding the fellowship across Ethiopia. Our next level of growth will have to include conducting translational research at the regional sites. I'm hopeful IGCS, its partners, and Global GYN Oncology faculty will help us grow in this as well. We desperately need evidence-based science within the local context to drive oncology care globally. Thank you very much. Innovating Health International has made a huge difference in the lives of women suffering from breast and cervical cancer in the poorest country in the Western Hemisphere. Her phone, one kid, she didn't get operated on in 2017, and she couldn't afford a syphilis directly at that point. It's not bad news, it's not bad news today, OK? Why is that? Because we have a lot of girls who have a big tumour, we have a tumour at the bottom, and a lot of girls that I met today, who did chemotherapy, that they said they had a tumour, they examined it today, they didn't feel it at all yet. That means that tomorrow morning, if you want, they will operate on you, and the operation will be very simple, OK? That's what we were hoping for, OK? And there's a good chance that that's what's going to happen to you, OK? So there, even if it's in front of me, I want to see them, OK? On behalf of Innovating Health International and all of its volunteers, we are both honoured and humbled to accept the International Gynaecologic Cancer Society Distinguished Advocacy Award. I'm extremely excited today to be named the recipient of the 2020 Distinguished Advocacy Award by International Gynaecological Cancer Society. My name is Ron CCW Chidebe, Executive Director of Project Pain Glue. Our community work revolves around advocacy for women battling with cancer, helping indigent women who cannot afford to buy even pain drugs to have access to quality care. We are supporting, navigating, connecting these women battling with cervical cancer, cancer of the womb, breast cancer and other forms of cancer to have a second chance in life. My dear friend, Brittany, has been battling with metastatic cancer for the past seven years, and she's doing great till today. In 2017, when I first met her at a meeting in the United States, she said to me that her greatest fear is that if she will ever have the opportunity to see her grandchild. As a result of access to better care, Brittany was able to see her grandchild and will still be here to see many of our children. There are many Brittany's in sub-Saharan Africa who hoped to have another chance in life, but never had one. There are many Brittany who sold their farmland, houses and other valuable properties to get a second chance in life, but never had the opportunity. In Europe and North America, cervical cancer is a rare cause of cancer death among women. Conversely, 90% of global cervical cancer deaths every year occur in low- and medium-income countries like Nigeria due to poor access to human papillomavirus vaccine. In 2018, it was estimated that out of 570,000 women who developed cervical cancer, 311,000 died of this disease. 88% of these deaths occur in low- and medium-income countries like Nigeria. Today, we have a tool that is cervical cancer vaccine to save our women and girls from cervical cancer. Painfully, many girls in my community do not have access to this life-saving vaccine. Cervical cancer clearly explains the impact of global inequity on women's and girls' health. Cancer is not a woman's thing. Cancer is a human and health issue that require collective effort of everyone to control. Thanks to International Gynecological Cancer Society for honoring me with this award. I greatly appreciate it. I'm looking forward to a day that hundreds of cancer patients in my community will have a second chance in life. A day when women in my community will have access to clinical trials that they need. A day women in my community will have access to this medicine that they needed most to see their grandchildren. A day that millions of these girls will have access to HPV vaccine to prevent cervical cancer. No matter who you are, where you live, and your story, you have the potential to change your story and the story of generations to come. I strongly believe that we may not have the power to change the situations of the past, but we have the power to change the present and the future. The future is you and me. The power is advocacy. Let's keep speaking. Thank you so much. Hi, I'm Audra Moran, President and CEO of Ovarian Cancer Research Alliance. We are so incredibly grateful to IGCS for the Distinguished Advocacy Award this year, and we're so sorry we can't be there with you in person. But we recognize what an honor it is, and we wanted to thank you and to thank the selection committee. As the world's oldest and largest ovarian cancer charity, we recognize our responsibility to ensure that this disease receives as much recognition as it can. So this award is certainly important, and we are so, so grateful to you. Since 1994, OCRA has given out over $100 million in medical research grants to scientists around the world working to end ovarian cancer. We've trained medical professionals through our Survivors Teaching Students program. We've advocated on behalf of women and their families. We've advocated on behalf of increased federal funding in the United States. And we've collaborated with many of our partners around the globe. We're also a proud member of the World Ovarian Cancer Coalition, and we provide support and education to anyone going through a diagnosis as well as their family and loved ones. We see this as our shared goal and our shared mission with all of our other organizations around the world, and we are committed to collaborating and working together in whatever way we can to end this terrible disease. So again, we are incredibly grateful for any opportunity to talk about our work and to elevate the cause, and we just want to thank IGCS and the Selection Committee for this honor, and thank you. Be well and stay safe. Congratulations to all the IGCS Award winners. I am Pedro Ramirez, an editor-in-chief of the International Journal of Gynecological Cancer. The journal presents its awards in concert with either the IGCS or ESGO meeting. This year, I am pleased to be here to present during the IGCS meeting. First, I would like to announce the top 10 reviewers for the International Journal of Gynecological Cancer this past year. The associate editors and I feel it's important to acknowledge the outstanding work being done by these excellent reviewers. The winners of the 2020 Award for Best Reviewers are Glauco Baiocchi, Matthew Harkenreiter, Philip Harder, Payam Katebikashi, Fabio Martinelli, Koji Matsuo, Alejandro Rauhain, Pamela Solomon, Shannon Weston, and Jason Wright. We're extremely grateful for their outstanding contribution. We also have two awards we present annually. The Most Downloaded Manuscript Award, which is the award to the manuscript most downloaded from the website of the International Journal of Gynecological Cancer, with data provided by our publisher, and this year, its Updates and Management Algorithm for Neuroendocrine Tumors of the Uterine Cervix by Gloria Salvo. The other award is the Editor's Choice Award, which is determined jointly by me and the associate editors for the manuscript that has been the most impactful during this year. I am pleased to present this award to David Sibula for their manuscript titled The European Society of Gynecologic Oncology Quality Indicators for Surgical Treatment of Cervical Cancer. We will now hear from both of them. On behalf of all the co-authors of this manuscript, thank you so much. We are very and so honored of receiving this award, the most downloaded paper in 2019. Thank you to the International Journal. Thank you to ESGO and IGCS. Thank you to the gynecologic oncology community that considered our review article on high-grade neuroendocrine cervical carcinomas interesting. The main goal of this publication was to put together everything that is written in the literature so far on this rare tumor, but also giving some input of what we are doing at MD Anderson. We have a registry with more than 350 patients. The NECTOR is a Neuroendocrine Cervical Tumor Registry at MD Anderson. I want to thank on behalf of the NECTOR team, Naomi Gonzalez and Michael Fromovitz. The main goal of the manuscript has been reached. We wanted to help physicians around the world to diagnose, treat in primary setting or recurrence setting, to treat patients with this rare disease. I also want to thank all the patients. The main reason of all our research are the patients that consented and family members that consented to be included on the registry and the sorority, also the sisters, the sorority on small and large cell carcinoma, that they are the reason why we are doing this. There's a lot more manuscripts to come. Again, thank you very, very much for this award. That means a lot to us. Thank you. There are several aspects which I'd like to highlight about this paper. The first one is the purpose of quality indicators as such. It gives us an instrument to measure and audit our surgical performance. This is the idea behind. This project of quality indicator was a subsequent one after three European societies developed practice management guidelines for patients with cervical cancer, ESGO, European Guiding Oncology, Astro-European Radiation Oncology and AST, a European pathology. The credit for this whole project goes to 17 experts from 13 European countries and to almost 100 external reviewers who all contributed to this paper. Finally, on behalf of all authors, I'd like to sincerely thank to the editor-in-chief and the editorial boards for this effort, which we really appreciate and value. I hope this project and this paper will be found useful and practical for the professional community. Thank you. Thank you, Pedro and everyone. Very inspiring to all of us. Please join me in congratulating the 2020 recipients. This now concludes the opening ceremony. I would like to welcome Dr. Nicoletta Colombo from Milan, Italy, who will moderate our plenary session. Thank you, Roberto, and welcome, everyone, to Plenary 1, the opening session of the IGCS 2020 Annual Global Meeting. I am Nicoletta Colombo from the University of Milan-Vicovka and European Institute of Oncology in Milan, Italy, and I will be moderating this session. During the next 30 minutes, we will hear three abstract presentations followed by a brief distillation. There will be no time for question and answer segment during this plenary, but future sessions, we have time for questions from the audience. You can learn more about our session speakers by clicking on the speaker information tab on the right side of the screen. You can contact these speakers with the IGCS link chat within the meeting portal. Without further delay, I'd like to invite Professor Jonathan Lederman to present his abstract. Thank you very much for this introduction. I'd like to thank the IGCS for giving me and my co-authors the opportunity to present JAVELIN-100 at this plenary session. It is the first Phase III trial of a PD-L1 inhibitor, Avelimab, in the first-line treatment of advanced ovarian cancer. These are my disclosures. JAVELIN-100 is an open-label Phase III trial, first-line treatment in ovarian cancer. As previously reported, the trial did not meet its primary endpoint, crossing pre-specified futility boundaries. But here I'm going to report the results of ongoing biomarker studies in this trial. This is the trial schema. It's a three-arm study of 998 patients, comparing six cycles of standard carboplatin and paclitaxel chemotherapy, either with Avelimab maintenance or chemotherapy in combination with Avelimab, and then given as maintenance. Avelimab was given every two weeks for up to 24 months. Patients were randomized at diagnosis and could either have primary surgery or neoadjuvant chemotherapy with interval debulking surgery, and either three-weekly or weekly paclitaxel, but no Bevacizumab was given. The primary endpoint, as you can see on the right, was progression-free survival, comparing the two Avelimab arms with standard chemotherapy, as assessed by independent radiological review. The patient characteristics were well-balanced, as you can see here. 40% of patients had neoadjuvant chemotherapy, and 25% of patients had some residual disease after primary surgery. The majority of patients, 75% or more, had high-grade serous ovarian cancer. The primary outcome at this interim analysis showed no benefit in progression-free survival for either of the two Avelimab arms compared with chemotherapy. You can see on the left that the median progression-free survival in the chemotherapy arm has not been reached, but it is 16.8 months and 18.1 months in the two experimental arms. Overall survival data are not mature, but there were more events in both the Avelimab arm and no suggestion of a survival benefit in favor of Avelimab. In looking at the toxicity in the three arms, we did not see any obvious toxicity signals for the addition of Avelimab to chemotherapy, although, as you see at the bottom, the discontinuation rates were higher in patients receiving Avelimab. Here, particularly, the Avelimab in chemotherapy is 63%. Sixty-three patients, 19%, had early discontinuation. Now moving on to the biomarker studies, and one of the most interesting ones and most often looked at is PD-L1 expression. Here we use the SB263 antibody to determine PD-L1 positivity. This was defined as a composite measurement of having greater than 1% of positive tumor cells and a population of greater than 5% of positive immune cells constituting PD-L1 positivity. We look now at the progression-free survival in the subgroup analysis by PD-L1 status, PD-L1 positive on the left, PD-L1 negative on the right. You can see that in these two groups, there was no effect of Avelimab in terms of outcome, although patients who are PD-L1 positive on the left did have a better outcome, better progression-free survival, than those that were PD-L1 negative. Similarly, looking at CD8 status, CD8 positive on the left, CD8 negative on the right, there appears to be no effect of Avelimab in relation to CD8 status. We then went on to look at the combination of CD8 positivity and PD-L1 positivity, looking both at patients who were positive for both biomarkers and those that were negative for both biomarkers and, of course, those who were positive for one and negative for the other. If we look now at these subgroup analysis of patients here, PD-L1 positive, CD8 positive, PD-L1 positive, and CD8 negative, we can again see that there is no obvious effect of Avelimab in either of these two subgroups. Similarly, PD-L1 negative and CD8 positive, and then the double negative, PD-L1 negative, CD8 negative, again, we see no emerging effect of Avelimab in any of the experimental groups. We also looked at germline BRCA status. About 10% of patients in this trial had mutations in BRCA1 or BRCA2, and as expected, their outcome was better. But again, looking at the effect of Avelimab in either the BRCA mutated or BRCA wild type, we could not see any signal of indicating that patients with Avelimab did better in any of those two groups. So, in conclusion, the JAVELIN-100 trial did not meet its primary objective of improving progression-free survival in either of the Avelimab arms compared to chemotherapy alone. We did not see any new safety signals, and the subgroup analysis based on PD-L1, CD8, and germline BRCA status did not identify any subsets of patients who had clear benefit in either of the Avelimab arms in this trial. Further biomarker studies are ongoing, including T-cell receptor sequencing and whole exome and RNA sequencing, which may help to characterize patients' immune response and variations in response to identify subsets that may be beneficial. And, of course, there are other ongoing first-line studies with immune checkpoint inhibitors, and we await those results with interest. Finally, I would just like to thank the patients and their families who contributed to this trial and all the co-investigators listed here from the 26 participating countries. Thank you. Thank you very much, Professor Lederman, for the very, very interesting presentation, and also thank you for being on time. We are perfectly on schedule. And now I would like to ask Dr. Antonio Gonzalez to present his abstract. So, please, Antonio, share your screen and begin your presentation. Thank you, Nicoletta, for this kind introduction. On behalf of my co-authors, I am presenting for the first time the efficacy and safety of lembatinib-plus-pembrolizumab in patients with previously treated advanced ovarian cancer included in the multi-cohort Phase II LIB005 study. We would like to thank the scientific committee for having selected our study for the plenary session. This is my disclosure. The background. Treatment options are very limited for patients with recurrent ovarian cancer and multiple prior lines of therapy, especially prognosis is poor for patients not eligible for platinum rechallenge, and there is a clear need for clinical trials to identify new active treatments. Pembrolizumab has shown antitumor activity as monotherapy in recurrent advanced ovarian cancer in the Phase II Keynode 100 study with increasing overall response rate at higher tumor PD-L1 expression. The combination of lembatinib, an antiangiogenic multi-kinase inhibitor, and pembrolizumab showed promising clinical activity in a prior Phase I-V2 study across several cancer types. The objective of our study was to evaluate the efficacy and safety of lembatinib plus pembrolizumab in patients with advanced ovarian cancer and three prior lines of therapy in one of the six cohorts of the Phase II LIB005 study. This slide shows the design of the ovarian cohort. Patients included in the study need to have advanced ovarian cancer, three prior lines of therapy, measurable disease according to RESIST 1.1 criteria, adequate performance status, and they provided tumor tissue for PD-L1 assessment. We used the CPS score to define positivity or negativity of the PD-L1 expression. 30 patients were planned to be included, although finally 31 patients were enrolled. The patients received pembrolizumab 200 milligrams intravenously every three weeks plus lembatinib 20 milligrams orally once a day. The treatment was given until progression or up to 35 cycles of therapy. The primary endpoints were overall response rate by blinded independent central review and safety tolerability. Another key secondary endpoints were disease control rate, duration of response, and progression-free survival also determined by a central review. In terms of patient disposition, 31 patients were recruited. As you can see in this slide, at the time of the data cutoff, with a median follow-up of 7.8 months, 48% of the patients were still on treatment. The most frequent reason for discontinuation was progression of disease in 39% of the patients. This table shows the baseline characteristics of our population. 71% of the patients had a performance status of ECOG 0. Most of the patients, 87%, had three prior lines of therapy, although three additional patients had four prior lines of therapy. Most of the patients, 81%, were considered platinum refractory or resistant according to the conventional classification. And many of the patients, 61%, had been previously exposed to Bevacizumab. Majority of our population had PD-L1 positivity in the tumor. And now let me show you the results. We observed a 32% response rate with a combination of pembrolizumab and lembadenib with a disease control rate of 74%. Remarkably, the response rate was 24% in platinum resistant and refractory patients and 21% in patients with prior exposure to Bevacizumab. Finally, 32% of the PD-L1 positive patients had an overall response rate. We also observed responses in the PD-L1 negative population. In this waterfall plot, you can see that most of the patients had a reduction in the target lesion size. As I said, both in the PD-L1 positive and also in the PD-L1 negative group of patients. The median duration of response has not been reached, and 83% of responders have a duration of the response of at least six months. And at the time of the data cutoff, only one patient that respond has showed some progression. Remarkably, the median progression free survival in this highly pretreated population was 4.4 months, and the rate of progression free at six months was 47%. Finally, the safety profile of the combination was consistent with prior experience in other disease. 13% of the patient had some discontinuation of any of the drugs due to adverse event, and only one patient had a grade five event with death due to hypovolemic shock that was attributed to the medication. The most frequent adverse event were hypertension in 74%, fatigue in 52%, and hypothyroidism in 42% of patients, but most of them were grade one or two. The rate of grade three and four was consistent with prior experience with this combination. Hypertension was seen in 19% of patients and fatigue in 10% of the patients. To conclude, limbotinib plus pembrolizumab demonstrated encouraging anti-tumor activity in patients with advanced ovarian cancer and failure of three or more prior lines of therapy, with an overall response rate of 32% and a disease control rate of 74%. It should be highlighted that we observed 24% response rate in patients with platinum, refractory, or resistant disease according to the conventional classification, and we also observed 21% of responses in patients previously exposed to bevacizumab. The median duration of response has not been reached, and the median progression free survival is 4.4 months with almost half of the patient without progression at six months. Limbotinib plus pembrolizumab had manageable toxicity in patients with advanced ovarian cancer with treatment-related adverse events leading to treatment discontinuation of one of the two drugs in 13% of the patients. Based on this data, this cohort will be expanded to 100 patients. Finally, I would like to thank the patients and their families, the investigators, and the staff for making possible this study. Thank you very much for your attention. Thank you, Dr. Gonzalez. That was really excellent. So the final abstract of this session is from Dr. Joanne Weber-Pauls. Joanne, please begin. Good afternoon. It's a pleasure to present the post-progression efficacy outcomes from the Phase 3 Arial 3 study of Rucaprib in patients with platinum-sensitive recurrent ovarian carcinoma associated with either a BRCA1 or BRCA2 mutation. The following are my author disclosures. It has been described that patients with advanced ovarian carcinoma associated with a BRCA2 mutation had longer overall survival following platinum chemotherapy than those with a BRCA1 mutation and those without either mutation. In Arial 3, Rucaprib maintenance for recurrent ovarian carcinoma significantly improved progression-free survival and post-progression efficacy outcomes versus placebo regardless of biomarker status. All post-progression efficacy outcomes were significantly longer with Rucaprib than placebo in the overall BRCA cohort. The present exploratory analysis of Arial 3 further examined the BRCA1 and BRCA2 mutant subgroups to assess the durability of the clinical benefit of Rucaprib maintenance following disease progression. Shown here is the study design of Arial 3, whereby eligible patients were sensitive to penultimate platinum therapy, responding with either a complete or a partial response. Included in the randomization stratification factors was mutation status by next-generation sequencing in BRCA1 or BRCA2. Patients were randomized 2 to 1 to oral Rucaprib 600 milligrams twice daily or placebo as maintenance. Post-progression efficacy endpoints were assessed in the subgroups of patients with a BRCA1 or BRCA2 mutation. In total, there were 196 patients enrolled. 117 patients had a BRCA1 mutation and 79 had a BRCA2 mutation. Overall, baseline characteristics and prior therapies were generally similar between the two groups. However, patients in the BRCA2 subgroup were slightly older and had a higher proportion with a partial response compared with a BRCA1 subgroup. Shown here are the post-progression outcomes, which assess if clinically meaningful improvements in progression-free survival can be maintained beyond the first progression event, delay the need for subsequent therapy, and persist across subsequent treatments. This slide represents the time to first subsequent therapy in the BRCA1 versus BRCA2 mutant subgroups. Median TFST was significantly longer with Rucaprib versus placebo in both subgroups. Yet, the treatment effect of Rucaprib was greater in the BRCA2 versus BRCA1 mutant subgroup with a median TFST of 30.4 months versus 16.8 months. Similarly, the median chemotherapy-free interval was longer with Rucaprib versus placebo in both subgroups. The treatment effect of Rucaprib was greater in the BRCA2 versus BRCA1 mutant subgroup with a CFI in the BRCA2 mutant group of 36.1 months, which is nearly double that in the BRCA1 mutant subgroup of 18.4 months. Shown here is the progression-free survival on subsequent line of therapy. And although both subgroups have a longer PFS2 with Rucaprib, the graph on the right shows that this is only significant in the BRCA2 subgroup. Similarly, the time to second subsequent therapy was longer with Rucaprib in both subgroups, yet the difference between Rucaprib and placebo was only significant in the BRCA2 mutant subgroup with a TSST of 34.2 months versus 19.4 months. Safety data for the two BRCA subgroups are shown here. Results were similar and consistent with previous reports, with the most common adverse events among Rucaprib-treated patients being nausea and dysthenia or fatigue, and the most frequent grade 3 toxicity being anemia. In conclusion, in this exploratory analysis, Rucaprib maintenance treatment led to a clinically meaningful delay in starting subsequent therapy and providing lasting clinical benefit versus placebo in patients with BRCA1 or BRCA2 mutant ovarian carcinoma. While both subgroups benefited, results suggest a greater benefit in patients with a BRCA2 mutation versus those with a BRCA1 mutation. Finally, the safety data for the two groups were similar and consistent with previous reports. I'd like to acknowledge all the investigators and Clovis and all the patients for their participation in ARIEL3. Thank you. Thank you very much, Dr. Weberfeld. I now invite Dr. Kathleen Moore from Oklahoma State University in the U.S. to provide a distillation of these three abstracts. Kathy, you have five minutes and she has a big challenge. I'm sure you will make it. Please, Kathy. Well, good day, everybody, and it's my great honor to have been asked to discuss these excellent abstracts. These are my disclosures. I think we can all agree at this point that our most validated predictive biomarker in epithelial ovarian cancer is BRCA, either in the germline or in the somatic testing. Here you see estimates that reflect the global incidence of having a tumor BRCA-associated cancer of 22%. Dr. Weberfeld, I'm going to go in a little bit of reverse order, has added to the strength of knowledge surrounding this predictive biomarker with the two main things that she summarizes in her presentation. One is more granularity around BRCA1 and BRCA2, and the second is around secondary endpoints. Starting with BRCA1 versus 2, she does present what we've all learned, is that patients with BRCA2-associated cancers do appear to do probably substantially better with platelet-based chemo, but also with PARC inhibitor exposure, than their BRCA1 counterparts. This is consistent with what we know from SOLA1 and from PRIMA, but I guess the question would be, what's missing is, so what? What do I do with that? Are we getting enough information around this group of mutations that we would potentially deescalate maintenance because they do so well? Or is it just good information to know, and it makes us feel better about that group of patients and we still treat them the same? I'm not arguing for either one of those, but I do want to know what I'm going to do with this information, and I think that remains to be discovered. The second thing she goes into is the secondary endpoints around ARIEL3, which are really of particular importance in maintenance and certainly PARC maintenance, because we're all interested in what happens in the next line of therapy after we expose a patient to a PARC inhibitor, either in the front line, which is becoming more common, or in the second line, platinum-sensitive setting. Her data adds, again, to the literature. I've just used SOLA1 and SOLA2, and I made some corresponding bar graphs for the data just presented from ARIEL3. Very consistent improvements in all secondary endpoints, and now we have some granularity around the superior expectations of BRCA2, but again, what's missing here? This is from her presentation, and I actually like this graphic with the definitions of secondary endpoints, but what I really want to know is not PFS2, which is measured from the time of starting ARIEL2 or whatever PARC until the next line of therapy, and you progress from that. I want to know PFS2 minus PFS1 for each group. How do you actually do when you are exposed to a prior PARC versus someone who's not on your next line of therapy? Do you do the same or better? I don't know that yet, and so that's really what I want to know from this study. I want to know overall survival. I know it wasn't an analytic endpoint in ARIEL3, but certainly we are collecting it, and I would like to know that data. And third, I think we have to remind ourselves with secondary endpoints with these PFS2, with looking at the second and third therapies and time to progression, those aren't prescribed measurement points. We're not dictating how often CTs are done or CO125s are measured or what constitutes a progression, and so we have to acknowledge some uncertainty around these endpoints as they probably reflect clinical practice, which is good, but aren't the same as strict clinical trials. So I think there's some questions here around the secondary endpoints. Moving on to immune checkpoint inhibitors by Dr. Letterman, we've now had two randomized phase three studies incorporating immune checkpoint inhibitors without PARC inhibitors into frontline ovarian cancer, and both were negative, and so I think our enthusiasm to say the least is a little bit dampened. This is JAVLIN100, and then you'll hear IMAGINE50 at ESMO. They're similar but different. For JAVLIN100, PD-L1 status was assessed but was not a stratification factor, and what you're seeing or what you saw today was the exploratory analyses trying to see whether or not there was a subgroup based on PD-L1 or other immune markers that would identify patients who would respond better to incorporation of an immune checkpoint inhibitor, but it didn't seem to work. And so here's one of the PFS curves that Dr. Letterman just shown you, and I think the question here is what's missing, and I think what's missing is we don't really know what PD-L1 positivity for ovarian cancer even means. This is the graphic from Dr. Letterman's talk with about 60% of patients being PD-L1 positive. If you add in CD8, it's probably 70%, and again, you'll see the data at ESMO for IMAGINE50, but they define PD-L1 positivity by this definition of PD-L1 greater than 1% and or PD-L1 immune cells greater than 5%, but where did this come from? It came from lung cancer, and so what do we know about PD-L1 positivity in ovary cancer? I'm just going to remind you about Kino100. This is by Ursula Matulonis, where they did combined positivity score, and they found this combined positivity score greater than 10 was associated with improved overall survival in a completely different population, but it just goes to show us that we're using all these different biomarkers for use of immune checkpoint inhibitors, and we don't even have a validated one for ovarian cancer. If you look at this table in the upper left, this is everything you can do for lung cancer. On the bottom of this slide, you have combined positivity score. That was Kino. You can use tumor proportion score, but the point is we have no unified standard in terms of technique or antibodies or scoring methods or cutoffs for ovarian cancer, and until we figure that out, we're really hard-pressed to design another big study that exposes women with ovarian cancer to immune checkpoint inhibitors unless we have some way to identify who is going to benefit, and hopefully that will become more evident with combination of data from JAVR1-100 as well as Imagine50 forthcoming, and then while we have immune biomarkers on the mind, we turn to the Lebo05, nicely presented by Dr. Antonio Gonzalez, so this is a small study. It's only 31 patients who received three lines of therapy, but a 32% response rate is really pretty respectable if you think that the historical benchmark is 10 to 15%, and so that confidence interval around 32%, that lower number is 17. That excludes that historical benchmark, making that really a promising target to move forward potentially in this high-end met need. That waterfall plot reminds me of this waterfall plot from LenPem in endometrial cancer where not everyone has a rhesus response, but almost everyone has some tumor shrinkage, and this of course led to the FDA approval of this combination in the United States with global approvals pending, but even here where you look at a biomarker-enriched population of PD-L1, you did see a signal, wide confidence intervals, but you did see a signal of superior response rate in those patients who are PD-L1 positive, and so this may warrant further explanation or exploration. What's missing here? More patients, more clarity around who benefits. Is this a regimen we select empirically? Your fourth line, you get this, or does it have biomarker direction, and I think that will come with more patients in a bigger study. I thank you for your attention and congratulations to the authors. Thank you very much, Dr. Moore. It was great to hear from all of you, and congratulations on your important work. Unfortunately, we do not have time for questions from the audience. I must move on to Plenary 2. Those of you who are watching, please be aware that you can contact the speakers via IGCS link chat here within the meeting portal to ask them any questions or to find out more information about these studies.

Avelumab

advanced ovarian cancer

progression-free survival

Lembatinib

Pembrolizumab

recurrent ovarian cancer

Rucaprid

BRCA1 mutations

BRCA2 mutations