5586 Background: Ovarian clear cell carcinoma (OCCC) is a histologically aggressive subtype of epithelial ovarian cancer with limited effective treatment options, particularly for recurrent disease. This study aims to evaluate the efficacy and safety of surufatinib (a kinase inhibitor targeting VEGFR 1, 2, 3, FGFR 1, and CSF-1R) in combination with toripalimab (an anti PD-1 antibody) for recurrent OCCC. Here, we present the latest efficacy and safety data. Methods: 23 patients aged 18-75 with histologically confirmed recurrent OCCC, ECOG performance status of 0-2, and failed first or subsequent-line therapy was enrolled (If the patient only had first line chemotherapy, platinum-free interval should be less than 12 months or disease progression occurred during chemotherapy). Patients received orally surufatinib 250 mg once daily in combination with toripalimab 240 mg on day 1 every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint is progression-free survival (PFS), and secondary endpoints include objective response rate (ORR), overall survival (OS), and safety. Results: From Jul. 2023 to Dec. 2025, 19 patients (median age 51) were enrolled, with 52.6% (10/19) had an ECOG PS of 0, 73.7% (14/19) were classified as clinical stage of I-II. 57.9% (11/19) had received prior first-line treatment, while the remaining 8 patients had received twice or more. Eight patients had previously received bevacizumab. Among the 19 patients, 10 were platinum-resistant while 9 were platinum-sensitive. The primary metastatic sites were lymph nodes (8/19, 42.1%), lungs (6/19, 31.6%), pelvic cavity (6/19, 31.6%) and peritoneum (5/19, 26.3%). With a median follow-up of 7.1 months, the median PFS was 4.4 months (95% CI: 2.6-8.8). Tumor response was evaluable in 19 patients, with 1 complete response, 4 partial response and 11 had stable disease, resulting in an ORR of 26.3% (95% CI: 9.2-51.2%), and a disease control rate of 84.2% (95% CI: 60.4-96.6%). The most common (≥20%) treatment related adverse events (TRAEs) were hyperthyroidism (42.1%), proteinuria (36.8%), hypertension (36.8%), diarrhea (36.8%), anaemia (31.6%), rash (31.6%), increased TSH (26.3%), hypoalbuminaemia (21.1%), increased AST (21.1%) and increased ALT (21.1%). Grade 3 TRAEs (≥10%) were mainly hypertension (15.8%), increased AST (15.8%), increased ALT (10.5%). All of AEs were effectively controlled after temporarily discontinuing surufatinib or toripalimab, or reducing the dose of surufatinib, or receiving symptomatic treatment. There were no cases with fatal outcome. Conclusions: The combination of surufatinib and toripalimab exhibited potential clinical activity and tolerable toxicity in patients with recurrent OCCC. Clinical trial information: ChiCTR2400083672.

5559 Background: Initial results from our trial showed the anti-tumor activity and good tolerance of CDK4/6 inhibitor dalpiciclib combined with NSAIs in patients (pts) with ER+ R/M ovarian cancer and uterine neoplasms (SGO, 2024, #S283; IGCS, 2025, #397). Here, we report updated results. Methods: This single-center, single-arm, open label, phase 2 trial enrolled pts with ER+, R/M ovarian cancer and uterine neoplasms which met the following criteria: pretreated low-grade serous ovarian carcinoma (LGSOC), pretreated uterine endometrioid carcinoma (EC), uterine leiomyosarcoma (LMS), or untreated low-grade endometrial stromal sarcoma (LGESS). Pts received dalpiciclib (150mg po d1-21 q28d) and NSAIs (mainly letrozole 2.5mg po qd) until disease progression, unacceptable toxicity or consent withdrawn. The primary endpoint was 12-week progression-free survival (12wPFS) rate. A Simon’s two-stage design was used (one-sided α=0.05, power=80%), and the null hypothesis (P0=0.2) would be rejected if totally >10 of 33 pts achieved primary endpoints. Results: As the data cutoff (Jan 5, 2026), 35 pts with a median of one prior therapy for R/M disease were enrolled, including 11 with LGSOC, 15 with EC, 8 with LGESS and 1 with LMS. With a median follow-up of 11.4 months (range, 0.1-52.2), 22 of 29 efficacy-evaluable pts had reached the primary endpoint, with a 12wPFS rate of 75.9% (95% CI 56.5-89.7), suggesting the value of further investigation. Detailed efficacy results are shown in Table 1. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 82.9% (29/35) of pts, mostly neutrophil count decreased (71.4%), white blood cell count decreased (45.7%) and platelet count decreased (14.3%). Sixteen pts had dose reduction of dalpiciclib, mostly due to hematologic toxicities. No serious adverse events or treatment-related deaths occurred. Twelve pts were still on-treatment, with 3 pts treated for >4 years. Conclusions: The trial achieved its positive primary endpoint, showing meaningful efficacy of dalpiciclib + NSAIs in ER+ R/M ovarian cancer and uterine neoplasms. No new safety signals were observed. Clinical trial information: ChiCTR2000040597. Efficacy results of evaluable pts. OverallN=29 LGSOCn=9 ECn=11 LGESSn=8 LMSn=1 12wPFS rate[95%CI] 75.9% (22/29)[56.5-89.7] 77.8% (7/9)[40.0-97.2] 63.6% (7/11)[30.8-89.1] 100% (8/8)[63.1-100] 0% (0/1)[0-97.5] Clinical Response Partial response (PR) 5 (17.2%) 1 (11.1%) 2 (18.2%) 2 (25.0%) 0 (0%) Stable disease (SD) 17 (58.6%) 6 (66.7%) 5 (45.5%) 6 (75.0%) 0 (0%) SD≥24 weeks 14 (48.3%) 5 (55.6%) 4 (36.4%) 5 (62.5%) 0 (0%) Progressive disease (PD) 7 (24.1%) 2 (22.2%) 4 (36.4%) 0 (0%) 1 (100%) ORR (CR+PR, 95% CI) 17.2% (5.85-35.8) 11.1% (0.28-48.3) 18.2% (2.28-51.8) 25.0% (3.19-65.1) 0% (0-97.5) CBR (CR+PR+SD≥24 weeks, 95% CI) 65.5% (45.7-82.1) 66.7% (29.9-92.5) 54.5% (23.4-83.3) 87.5% (47.4-99.7) 0% (0-97.5)

Recurrent ovarian clear cell carcinoma (OCCC) remains a therapeutic challenge due to intrinsic chemoresistance and paucity of targeted options. Surufatinib is a multi-target tyrosine kinase inhibitor that may enhance antitumor immunity when combined with PD-1 blockade. We report a 53-year-old female with recurrent OCCC who developed a platinum-sensitive first relapse (platinum-free interval, 9.8 months) after adjuvant platinum-based chemotherapy and achieved a 24-month progression-free survival (ongoing) on surufatinib plus toripalimab. The best response was partial response, and treatment was well tolerated except for Grade 1 hemoptysis and Grade 1–2 proteinuria. Radiologic disease control was durable. However, because biomarker assessment relevant to immune checkpoint inhibition was not performed, the biological basis of response remains uncertain. This case suggests the clinical feasibility of surufatinib plus toripalimab and its association with durable disease control in an individual patient with recurrent OCCC. However, given the platinum-sensitive nature of the relapse, treatment efficacy should be interpreted cautiously. Further prospective studies incorporating biomarker assessment are warranted.

OBJECTIVE:Early-stage uterine leiomyosarcoma (uLMS) remains a clinical challenge due to high recurrence and mortality rates. As most early-stage cases are diagnosed at stage IB, this study aims to investigate the prognostic factors and optimal management for stage IB uLMS. METHODS:A retrospective review was conducted of medical records for patients who underwent surgical intervention and were diagnosed with stage IB uLMS at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from January 1, 2006, to August 31, 2023. RESULTS:After a median follow-up time of 70.1 months (range: 2.3-234.1), we observed a median disease-free survival (DFS) of 18 months and overall survival (OS) of 67.9 months, respectively. Median DFS was 14.7 months in the observation group and 18.4 months in the adjuvant chemotherapy group. Median OS was 75.4 months in the observation group and 66.6 months in the adjuvant chemotherapy group. Five-year DFS rates were 14.1% and 15.7%, and OS rates were 66.5% and 54.1% for the observation and chemotherapy groups, respectively. Poor DFS was associated with age >48 years, postmenopausal status, tumor size >12 cm, elevated Ki-67 levels, and lymphadenectomy, but these factors did not correlate with OS outcomes. No significant DFS or OS differences were found between chemotherapy and observation groups or across chemotherapy regimens. Ovarian preservation did not affect prognosis. CONCLUSION:Age >48 years, postmenopausal status, larger tumor size, higher Ki-67, and lymphadenectomy predicted poor DFS but not OS in stage IB uLMS. Ovarian preservation is safe. Adjuvant chemotherapy with different regimens showed no significant survival benefits.

5516 Background: The first stage results of a Simon’s two-stage single-arm phase II trial showed promising antitumor activity and manageable safety of camrelizumab (a humanized anti-PD-1 monoclonal antibody) plus apatinib (a highly selective VEGFR2 inhibitor) in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy. Here, we report the primary results of this trial. Methods: This open-label, single-arm, phase II trial used a minimax Simon’s two-stage design. Patients with advanced or recurrent endometrial cancer that had progressed after at least one prior systemic therapy were treated with camrelizumab (200 mg, intravenously, every two weeks) and apatinib (250 mg, orally, daily) on a four-week cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other assessed endpoints were disease control rate, time to response, duration of response, time to treatment failure, progression-free survival, overall survival, and treatment-related adverse events. Results: Between January 20, 2020 and October 14, 2022, 36 patients (median age: 60 [range: 29, 76] years; 17 [47.2%] had Eastern Cooperative Oncology Group [ECOG] performance status 1; 15 [41.7%] had received at least two prior systemic therapies) were enrolled. At the date of data cutoff (December 31, 2022), the median follow-up time was 13.9 (interquartile range: 5.8-23.2) months. All 36 patients were evaluable for efficacy, the confirmed objective response rate was 44.4% (95% CI: 27.9%, 61.9%) and the conformed disease control rate was 88.9% (95% CI: 73.9%, 96.9%), with two complete response, 14 partial response, and 16 stable disease. The median progression-free survival was 6.4 (95% CI: 5.2, 13.0) months. The treatment-related adverse events of grade 3 or greater occurred in 19 (52.8%) patients, with increased gamma-glutamyltransferase (8 [22.2%]), hyperglycemia (4 [11.1%]), hypertension (4 [11.1%]) and increased direct bilirubin (4 [11.1%]) being most common. Reactive cutaneous capillary endothelial proliferation occurred in 6 (16.7%) patients and all were grade 1 or 2. No treatment-related death occurred. Conclusions: Camrelizumab plus apatinib show promising antitumor activity and manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy and warrant further investigation. Clinical trial information: ChiCTR2000031932 .

BackgroundNeoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC.MethodsEligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m2, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations).ResultsSixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively.ConclusionsThe study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting.Trial registrationClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019.

Introduction Ovarian clear cell carcinoma (OCCC) has distinct clinical and molecular features and heterogeneous prognosis. Insights into the somatic genomic abnormalities of OCCC provide the basis for deeper understanding and potential therapeutic avenues. Herein, we performed extensive genomic profiling in Chinese patients to illustrate the mutation landscape and genetic prognostic biomarkers of OCCC. Patients and methods We used targeted DNA sequencing on 61 OCCC cases with a panel of 520 cancer-related genes. Correlations between clinicopathological features and survival were evaluated. Nomogram-based models were constructed to predict progress-free survival (PFS). Results We detected 763 somatic mutations spanning 286 genes. The most frequent genetic alterations, ARID1A (49%) and PIK3CA (48%), were concurrently mutated. Comprehensive copy number alterations (CNAs) were identified in chromosomes 20q13.2 and 8q. Most (73.7%) patients harboured potentially targetable driver mutations. The mean and median tumour mutational burden were 7.0 and 3.0 mutations/Mb, respectively. Microsatellite instability (high) was identified in 8.2% of patients. Mutation of the base-excision repair pathway was significantly higher in patients of stage II/III/IV. ATM mutation was associated with platinum sensitivity (p < .05). Survival analysis identified chr8q CNAs in all patients, PIK3CA mutations in stage I patients and SWI/SNF complex (ARID1A and SMARCA4) mutations in stage II/III/IV patients as potential prognosticators (p < .05). Integration of genetic alterations (SWI/SNF complex mutations, ATM mutations and chr8q CNAs) improved the performance of a nomogram based on tumour stage and residual disease (concordance index 0.75 vs. 0.70, p < .05). Conclusions We described somatic genomic alterations in Chinese OCCC patients and observed different genomic alterations between stage I and stage II/III/IV tumours. Genetic factors may supplement clinical factors in nomogram modelling for PFS prediction. Key Messages We performed extensive genomic profiling in a well-annotated cohort of 61 Chinese ovarian clear cell carcinoma (OCCC) patients. PIK3CA mutations were associated with worse overall survival (OS) in stage I OCCC, and SWI/SNF gene mutations were associated with improved OS in stage II/III/IV disease. We propose an easy-to-use nomogram using clinical factors (tumour stage and residual disease) and genetic alterations (SWI/SNF complex mutations, ATM mutations and chr8q CNAs) to predict the progress-free survival (PFS) of OCCC.

IntroductionThis study aimed to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-p) combined with carboplatin as a neoadjuvant chemotherapy (NACT) regimen for patients with ovarian cancer (OC).MethodsThis is a single-center, open phase Ib/II Clinical Trial (ChiCTR1900026893). We enrolled women with unresectable epithelial OC, FIGO stage III or IV. Patients received 3 cycles of NACT, then interval debulking surgery (IDS), followed by 3–6 cycles of adjuvant chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 plus nab-p 260 mg/m²(Keaili®). In the phase II part, the primary objective was R0 resection rate(figure 1).ResultsPhase Ib results showed the NACT was safe and tolerable, so the study proceeded to phase II. A total of 50 patients were included in this analysis, 10 patients in the phase Ib and 40 patients in the phase II. Twenty-nine (58%) patients had stage IV. All patients completed planned NACT and 8 (16%) patients experienced delayed chemotherapy due to adverse events (AE). After NACT, the objective response rate was 81.3% (95%CI: 67.4%-91.1%) in 48 patients who had at least one tumor assessment. Among the 45 patients who underwent IDS, 5 patients (11.1%) had surgery delayed due to AE, all patients achieved optimal debulking and 77.8% (95%CI: 62.9%-88.8%) achieved R0 resection. During NACT, the most common grade 3/4 AEs were hematologic toxicities, including neutropenia (78%), leucopenia (48%) and thrombocytopenia (24%). All AEs returned to normal or acceptable levels after receiving appropriate treatment.Conclusion/ImplicationsNab-p plus carboplatin as a NACT regimen was effective and tolerable for unresectable epithelial OC.

Peritoneal implantation and lymph node metastasis have different driving mechanisms in ovarian cancer. Elucidating the underlying mechanism of lymph node metastasis is important for treatment outcomes. A new cell line, FDOVL, was established from a metastatic lymph node of a patient with primary platinum-resistant ovarian cancer and was then characterized. The effect of NOTCH1-p.C702fs mutation and NOTCH1 inhibitor on migration was evaluated in vitro and in vivo. Ten paired primary sites and metastatic lymph nodes were analyzed by RNA sequencing. The FDOVL cell line with serious karyotype abnormalities could be stably passaged and could be used to generated xenografts. NOTCH1-p.C702fs mutation was found exclusively in the FDOVL cell line and the metastatic lymph node. The mutation promoted migration and invasion in cell and animal models, and these effects were markedly repressed by the NOTCH inhibitor LY3039478. RNA sequencing confirmed CSF3 as the downstream effector of NOTCH1 mutation. Furthermore, the mutation was significantly more common in metastatic lymph nodes than in other peritoneal metastases in 10 paired samples (60% vs. 20%). The study revealed that NOTCH1 mutation is probably a driver of lymph node metastasis in ovarian cancer, which offers new ideas for the treatment of ovarian cancer lymph node metastasis with NOTCH inhibitors.

OBJECTIVE:This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS:In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS:33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION:Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

Background We performed an integrative genomic and transcriptomic profiling to identify molecular subtypes and prognostic markers with special focus on immune-related pathways. Methods Totally, 50 Chinese patients were subjected to targeted next-generation sequencing and transcriptomic sequencing. Results Two distinct subgroups were identified as immune (22.0%) and non-immune (78.0%) based on the immune-pathway related hierarchical clustering. Surprisingly, patients with immune subtype had a significantly worse survival. The prognostic capacity was validated in external cohorts. The immune group had higher expression of genes involved in pro-inflammation and checkpoints. PD-1 signalling pathway was enriched in the immune subtype. Besides, the immune cluster presented enriched expression of genes involved in epithelial-mesenchymal transition, angiogenesis and PI3K-AKT-mTOR signalling, while the non-immune subtype had higher expression of metabolic pathways. The immune subtype had a higher mutation rate of PIK3CA though significance was not achieved. Lastly, we established a prognostic immune signature for overall survival. Interestingly, the immune signature could also be applied to renal clear cell carcinoma, but not to other histologic subtype of ovarian cancer. Conclusions An immune subtype of OCCC was identified with poor survival and enrichment of PD-1 and PI3K-AKT-mTOR signalling. We constructed and validated a robust prognostic immune signature of OCCC patients.

Abstract Background The aim of the present study was to assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features. Methods Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 was performed on whole section slides, and the results were correlated with clinicopathologic variables. Results A total of 108 cases were included in the present study with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3 and 69.6%, respectively, of the total cases. Overall, the estimated 5-year overall survival was 70.3 and 20.7% in patients with early- and late-stage tumors, respectively. Deficient MMR was identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n = 4) and MLH1/PMS2 (n = 2). The average age of the six patients with deficient MMR was 45.6 years, and the rate of MMR-deficient tumors in women ≤50 years was relatively higher than that in women over 50 years (10.0% vs. 2.9%; P = 0.266). Half of the patients with deficient MMR were diagnosed with synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, which was significantly more than their intact counterparts (P = 0.002). All six patients with deficient MMR had early-stage tumors, and the majority (83.3%) were platinum sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than in their intact counterparts (30 months vs. 27 months), but significance was not achieved (P = 0.471). Conclusions Young ovarian CCC patients with concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors, thereby warranting additional studies to determine whether patients harboring MMR abnormalities have a favorable prognosis.

Background: In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC. Methods: We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model. Results: The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration >= 9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births. Conclusions: Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

5591 Background: For advanced or recurrent endometrial cancer (EC), therapeutic options remain scarce. Immune or antiangiogenic monotherapy has shown moderate efficacy in EC. Preclinical and clinical data showed that camrelizumab (an anti-PD-1 antibody) plus apatinib (a selective VEGFR2 inhibitor) markedly enhanced anti-tumor efficacy in multiple solid tumors. This study was designed to assess the efficacy and safety of the combination of camrelizumab and apatinib as second-line or above therapy for advanced or recurrent EC. Methods: This was an open-label, single-arm, phase II trial conducted in China. Patients with advanced or recurrent EC who progressed after at least first-line therapy received camrelizumab (200 mg, intravenously, q2w) plus apatinib (250 mg, orally, qd). Using a minimax Simon two-stage design, 21 patients were enrolled at stage I and if a complete or partial response was observed in at least four patients, the enrollment would be continued to 40 patients. The primary endpoint was the objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included time to objective response (TTR), disease control rate (DCR), duration of Response (DoR), progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF) and safety. Here, the results of stage I are reported. Results: Between January 20, 2020 and July 8, 2021, 21 patients were enrolled. The median age was 57 years (range 29–72). Thirteen patients (61.9%) had ECOG PS of 0, and eight patients (38.1%) received at least two prior therapies. As of November 9, 2021, the median follow-up time was 13.5 months (IQR 11.3-16.3). Among 21 evaluable patients, the confirmed ORR was 47.6% (95% CI 25.7%-70.2%) with complete response in one patient (4.8%) and partial response in nine patients (42.9%); eight patients had stable disease for a DCR of 85.7% (95% CI 63.7%-97.0%). The median PFS was 11.8 months (95% CI 5.2-14.4). Treatment-related adverse events (TRAEs) of any grade and of grade ≥ 3 were reported in 21 (100%) patients and 10 (47.6%) patients, respectively. The most common grade ≥ 3 TRAEs included gamma-glutamyltransferase increased (six [28.6%]), direct bilirubin increased (four [19.0%]), alanine aminotransferase increased (three [14.3%]), aspartate aminotransferase increased (three [14.3%]) and hyperglycaemia (three [14.3%]). Four patients (19.0%) experienced reactive cutaneous capillary endothelial proliferation, all of which were grade 1-2. No treatment-related deaths were reported. Conclusions: Camrelizumab plus apatinib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced or recurrent EC after failure of at least first-line therapy. Clinical trial information: ChiCTR2000031932.

Objective:This study was aimed to profile hotspot exonuclease domain mutations (EDMs) of the DNA polymerase ϵ gene (POLE) in endometrial cancer (EC) and to investigate the effects of EDMs on tumor cell behavior and catalytic activities of Polϵ.Methods:POLE sequencing was performed in tumor tissue samples from patients with EC to identify hotspot EDMs. Bioinformatics tools were used to select the potential pathogenic EDMs. The association of EDMs with the clinical outcomes of patients was assessed. EC cells were transfected with wildtype POLE or POLE variants to examine the effects of the EDMs on EC cell behavior, including cell cycle, migration, and invasion. Co-immunoprecipitation was employed to obtain FLAG-tagged wildtype and mutant catalytic subunits of Polϵ, followed by the assessment of polymerase and exonuclease activities.Results:In addition to previously reported P286R and V411L, R375Q and P452L were identified as novel, and deleterious POLE hotspot EDMs of EC. Patients in EDM group had significantly better clinical outcomes than the rest of the cohort. Compared with wildtype POLE, overexpression of POLE variants promoted cisplatin resistance, G0/G1 cell cycle arrest, and cell migration and invasion in EC cells. Overexpression of POLE variants significantly increased the abundance of 3'-OH and upregulated the expression of DNA mismatch repair genes in HEK293T cells. Compared with wildtype Polϵ, Pol ϵ mutants exhibited undermined polymerase and exonuclease abilities in the presence of mismatched nucleotides in HEK293 cells.Conclusion:We characterized the of hotspot exonuclease domain mutations in the DNA polymerase ϵ gene and identified P286R, V411L, R375Q, and P452L as pathogenic POLE hotspot EDMs in endometrial cancer. These hotspot EDMs are associated with the malignant behavior of endometrial cancer cells in vitro and favorable prognosis in patients, suggesting that POLE affects a wide range of cellular processes beyond DNA replication and proofreading.