Jianqing Zhu

Fuzuloparib with or without apatinib as maintenance therapy in newly diagnosed, advanced ovarian cancer (FZOCUS‐1): A multicenter, randomized, double‐blind, placebo‐controlled phase 3 trial

Abstract Although poly(adenosine diphosphate‐ribose) polymerase inhibitors (PARPis) and bevacizumab were approved as first‐line maintenance for advanced ovarian cancer (OC), evidence comparing this combination with PARPi monotherapy, especially in BRCA ‐mutated/homologous recombination‐deficient (HRD) patients, is lacking. This study compared combined fuzuloparib (a PARPi) plus apatinib (a vascular endothelial growth factor receptor‐2 inhibitor) with either fuzuloparib or placebo as first‐line maintenance in patients with advanced OC. Patients who had newly diagnosed, advanced OC and responded to first‐line, platinum‐based chemotherapy were randomized 2:2:1 to receive combined fuzuloparib (100 mg twice daily) plus apatinib (375 mg daily), fuzuloparib (150 mg twice daily) plus placebo, or double‐placebo treatment. The primary end point was blinded independent review committee (BIRC)‐assessed progression‐free survival (PFS). Six hundred seventy‐four patients were randomized to receive fuzuloparib plus apatinib ( n  = 269), fuzuloparib ( n  = 269), or placebo ( n  = 136). At the final analysis (November 1, 2024; 385 BIRC‐assessed PFS events; median follow‐up, 40 months), the median BIRC‐assessed PFS was 26.9 months with the combination versus placebo (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44–0.75; one‐sided p  < .0001) and 29.9 months with fuzuloparib monotherapy versus placebo (HR, 0.58; 95% CI, 0.44–0.75; one‐sided p  < .0001) compared with 11.1 months with placebo. A PFS benefit was observed regardless of germline BRCA1/2 mutation status. In homologous recombination‐deficient patients (including those with BRCA1/2 mutations), combined fuzuloparib and apatinib produced a PFS similar to that of fuzuloparib (34.1 vs. 35.8 months, respectively); in homologous recombination‐proficient patients, PFS had a trend favoring the combination (16.6 vs. 11.0 months; HR, 0.73; 95% CI, 0.45–1.19). Both treatments were well tolerated. Overall survival was immature. Both fuzuloparib and combination therapy improved PFS compared with placebo as maintenance therapy for patients who had newly diagnosed, advanced OC. Adding apatinib to fuzuloparib did not prolong PFS among homologous recombination‐deficient patients. There was a PFS benefit trend among homologous recombination‐proficient patients who received combination therapy compared with those who received monotherapy.

Personalized Cancer-Specific Protein-Aptamer Corona for Orthogonal Multiplex Cancer Diagnosis

Aptamers are powerful synthetic recognition elements for biosensing, yet their application in complex biofluids, such as human serum, is critically limited by enzymatic degradation. To overcome this fundamental challenge, we introduce a novel analytical platform centered on the concept of a personalized protein-aptamer corona (PAC). This strategy leverages the spontaneous formation of a disease-specific protein corona on magnetic nanoparticles, which not only enriches low-abundance biomarkers but also creates a stabilized, nuclease-free nanobio interface for subsequent aptamer recognition. The integration of this PAC concept with an 8-channel orthogonal multiplexed electrochemical (OMEC) chip enables sensitive, amplification-free (PCR-free) signal transduction via alternating current voltammetry. By coupling this platform with machine learning algorithms, we translate complex, multiplexed aptamer binding signatures into a robust diagnostic output. Clinical validation on two independent cancer cohorts demonstrated outstanding performance, achieving an area under the curve of 99.50% for ovarian cancer (

Spatially resolved proteomics surveys the chemo‐refractory proteins related to high‐grade serous ovarian cancer

AbstractHigh‐grade serous ovarian carcinoma (HGSC) is a lethal malignancy characterized by high incidence, mortality, and chemoresistance. However, its molecular drivers are unknown. In this study, spatially resolved proteomics was applied to 1144 formalin‐fixed paraffin‐embedded tissue spots obtained by laser capture microdissection from 10 patients with HGSC and divergent carboplatin‐paclitaxel (CP) responses. Specific sampling revealed stroma‐driven tumour heterogeneity, identifying 642 tumour‐specific and 180 stroma‐specific proteins, with 505 CP‐responsive therapeutic targets. Most of these protein signatures represented previously unreported associations with chemoresistance in HGSCs. Two clinically significant spatial proteomic maps were generated by introducing tumour (TS) and chemical (CS) scores. TS analysis revealed conserved tissue architecture across CP response groups, whereas CS mapping revealed pretreatment metabolic reprogramming (rather than proliferation) as the defining feature of chemo‐resistant tumours, challenging current resistance paradigms. Immunohistochemical validation of HGSC tissue microarrays confirmed the spatial proteomic localization of TFRC and PDLIM3, which are linked to tumour progression, while establishing their novel role as chemotherapy resistance biomarkers through this study, with broader predictive potential observed across additional targets in the discovery cohort. This study developed a spatially resolved proteomic framework to enhance the diagnostic and therapeutic strategies for HGSC.Key points HGSC intra‐tumour heterogeneity is predominantly driven by stroma, as revealed by spatial proteomic compartmentalization (tumour/stroma). Spatial proteomics expands the therapeutic target database, enabling prediction of platinum‐based chemotherapy response. Chemo‐resistant patients exhibit pre‐treatment metabolic activation rather than proliferative signatures. TFRC (iron transport) and PDLIM3 (cytoskeletal remodelling) are spatially validated as chemo‐response biomarkers.

Proteomic landscape of epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Sentinel lymph Node mapping versus systematic pelvic lymphadenectomy on the prognosis for patients with intermediate-high-risk Endometrial Cancer confined to the uterus before surgery: trial protocol for a non-inferiority randomized controlled trial (SNEC trial)

Sentinel lymph node (SLN) mapping has been recommended as an alternative staging approach to lymphadenectomy for apparent uterine-confined endometrial cancer (EC). However, the prognostic value of SLN mapping alone instead of systematic lymphadenectomy on EC patients remains unclear. A multi-center, open label, non-inferiority randomized controlled trial has been designed to identify if SLN mapping alone is not inferior to pelvic lymphadenectomy on prognosis of patients with intermediate-high-risk EC clinically confined to uterus. Eligible patients will be 1:1 randomly assigned to accept SLN mapping or pelvic lymphadenectomy. The primary endpoint is the 2-year progression-free survival (PFS). The second points are the 5-year PFS, 5-year overall survival, surgery-related adverse events and life quality. A total of 780 patients will be enrolled from 6 hospitals in China within 3-year period and followed up for 5 years. ClinicalTrials.gov Identifier: NCT04276532.

Pulmonary metastasectomy for recurrent metastatic ovarian cancer

AbstractAimThe prognosis of patients with ovarian cancer with lung metastasis is poor; data on pulmonary metastasectomy for such patients are lacking. This study aimed to determine the safety and feasibility of pulmonary resection as part of cytoreductive surgery for recurrent metastatic ovarian cancer.MethodsMedical records of patients with ovarian cancer, who underwent pulmonary resection for lung metastasis in our hospital from April 2012 to February 2022, were retrospectively reviewed.ResultsTen patients were included (median age, 53 years). Five patients had metastatic disease limited to the lungs. Additional surgeries included diaphragm resection, partial hepatectomy, para‐aortic lymph node dissection, and cytoreduction. We achieved complete cytoreduction for all patients without severe complications, and the 30‐day mortality was zero. After a median follow‐up of 23 months, four of the patients experienced recurrence. One patient recurred 9 months after the operation and was lost to follow‐up at 17 months, two died at 68 and 26 months respectively, one is alive with disease (23 months), and six are alive without recurrence, among whom two have survived for 56 and 124 months.ConclusionsPulmonary resection for recurrent metastatic ovarian cancer seems safe and feasible, with long‐term survival observed in certain patients. Pulmonary metastasectomy can be performed as part of the debulking surgery for selected patients with relapsed metastatic ovarian cancer. Both the patient lost to follow‐up and the one who died at 26 months, had two lung metastatic nodules and did not receive postoperative chemotherapy, which might have led to relatively poor prognosis.

Resistance prediction in high‐grade serous ovarian carcinoma with neoadjuvant chemotherapy using data‐independent acquisition proteomics and an ovary‐specific spectral library

High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P  = 0.002). The classifier was validated with 57 patients from an independent clinical center ( P  = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment.

A phase II trial of cytoreductive surgery combined with niraparib maintenance in platinum-sensitive, secondary recurrent ovarian cancer: SGOG SOC-3 study

In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography-computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cycles of platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate. ClinicalTrials.gov Identifier: NCT03983226.

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline BRCA1/2 Mutation and Platinum-sensitive Recurrent Ovarian Cancer

Abstract Purpose: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. Patients and Methods: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. Results: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5–18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6–78.2] and 70.8% (95% CI, 61.5–79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3–13.9) and 10.3 months (95% CI, 9.2–12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2–96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. Conclusions: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial

PURPOSE This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA)

Abstract Purpose: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer. Patients and Methods: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan–Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453). Results: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs. Conclusions: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201

Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study

Background Combination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial. Methods Eligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator’s assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile. Results Of the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8–4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0–23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator. Conclusion The camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration. Trial registration number NCT03827837.

Pamiparib Monotherapy for Patients with Germline BRCA1/2 -Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study

Abstract Purpose: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer. Patients and Methods: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1. Results: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34–79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2–21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3–74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6–56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count. Conclusions: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile.

A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma

AbstractThis phase 2 study assesses the efficacy and safety of camrelizumab (an anti-PD-1 antibody) plus famitinib (anti-angiogenic agent) in women with pretreated recurrent or metastatic cervical cancer (ClinicalTrials.gov NCT03827837). Patients with histologically or cytologically confirmed cervical squamous cell carcinoma experiencing relapse or progression during or after 1–2 lines of systemic therapy for recurrent or metastatic disease are enrolled. Eligible patients receive camrelizumab 200 mg intravenously on day 1 of each 3-week cycle plus famitinib 20 mg orally once daily. The primary endpoint is the objective response rate. Secondary endpoints are duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. The trial has met pre-specified endpoint. Thirty-three patients are enrolled; median follow-up lasts for 13.6 months (interquartile range: 10.0–23.6). Objective responses are observed in 13 (39.4%, 95% confidence interval [CI]: 22.9–57.9) patients; the 12-month duration of response rate is 74.1% (95% CI: 39.1–90.9). Median progression-free survival is 10.3 months (95% CI: 3.5–not reached) and the 12-month overall survival rate is 77.7% (95% CI: 58.9–88.7). All patients experience treatment-related adverse events; grade ≥3 events occur in 26 (78.8%) patients. Treatment-related serious adverse events and deaths are observed in 9 (27.3%) and 2 (6.1%) patients, respectively. Camrelizumab plus famitinib shows promising antitumor activity with a manageable and tolerable safety profile in patients with pretreated recurrent or metastatic cervical squamous cell carcinoma. This combination may represent a treatment option for this population.

Efficacy and safety of zimberelimab (GLS-010) monotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, single-arm, phase II study

There is an unmet need to improve clinical outcomes for patients with recurrent/metastatic cervical cancer. Checkpoint inhibitors represent a promising treatment strategy. We evaluated the safety and anti-tumor activity of zimberelimab, an anti-programmed cell death protein-1 antibody, in patients with previously treated, recurrent, metastatic cervical cancer. This phase II, single-arm, open-label study used a Simon two-stage minimax design. Eligible patients were women aged 18-75 years with programmed death ligand-1-positive recurrent or metastatic cervical cancer that had progressed after first- or subsequent-line chemotherapy (Eastern Cooperative Oncology Group (ECOG) performance status 0-1). Patients received intravenous zimberelimab (240 mg every 2 weeks) for 2 years until disease progression, intolerable adverse effects, or withdrawal from the study. The primary endpoint was objective response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, by an independent review committee. A total of 105 patients were enrolled. Median age was 51 (range, 31-75) years; 63.8% had an ECOG performance status of 1. The median number of previous treatment lines was 1 (range, 1-4). Median follow-up was 16.9 (range, 16.3-18.4) months. The objective response rate was 27.6%, and the disease control rate was 55.2%. Median duration of response was not reached. Median overall survival was 16.8 months, and median progression-free survival was 3.7 months. The incidence of treatment-related adverse events of any grade was 78.1%, of which the most common were hypothyroidism (26.7%) and anemia (19.0%). Zimberelimab monotherapy demonstrated durable anti-tumor activity and an acceptable safety profile in patients with cervical cancer. NCT03972722.

First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial

First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer. ClinicalTrials.gov Identifier: NCT03635489.

A Single-arm, Multicenter Clinical Study of Becotatug Vedotin Combined With Zimberelimab in the Treatment of Recurrent and Metastatic Cervical Cancer, Vulvar Cancer and Vaginal Cancer

This is a prospective, multicenter, single-arm clinical trial investigating Becotatug Vedotin in combination with Zimberelimab for the treatment of patients with recurrent and metastatic cervical cancer, vulvar cancer, and vaginal cancer. A total of 30 patients are expected to be enrolled. The study consists of a screening period (within 28 days), a treatment period, and a follow-up period (safety follow-up and survival follow-up). Trial treatment will continue until the patient has received Becotatug Vedotin for 1 year, or until disease progression, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. Subjects will sign the informed consent form and undergo baseline examinations during the screening period. Patients who meet the inclusion and exclusion criteria will enter the treatment period. All subjects will complete the relevant examinations specified in the protocol during treatment to observe safety, tolerability, and efficacy.

Surgery and Niraparib in Secondary Recurrent Ovarian Cancer (SOC-3 Trial)

This is a Phase II, open-label, multicenter, randomized umbrella study to evaluate the efficacy of cytoreductive surgery and Niraparib maintenance in participants with platinum-sensitive secondary recurrent ovarian cancer. Cohort 1 will focus on participants without prior use of PARP inhibitor, and without prior secondary cytoreduction (SCR) when first recurrence. Cohort 2 will focus on participants with prior use of PARP inhibitor, but without prior SCR when first recurrence. Cohort 3 will focus on participants with SCR when first recurrence, but without prior use of PARP inhibitor.

Study of GLS-010 Injection in Patients With Recurrent or Metastatic Cervical Cancer

Patients with recurrent or metastatic cervical cancer，and will be treated with GLS-010.

A Trial of Maintenance Treatment With Fluzoparib Versus Placebo in Relapsed Ovarian Cancer Patients

To evaluate the efficacy, safety tolerability of maintenance therapy with Fluzoparib(A PARP inhibitor) versus placebo in Chinese patients with recurrent ovarian cancer who achieved a complete response (CR) or partial response (PR) after platinum-based chemotherapy

Famitinib Plus Anti-PD1 Therapy for Advanced Urinary System Tumor, Advanced Gynecological Tumors

Phase II multi-chort, adaptive two-stage, open label, nonrandomized study. The aim of our study is to evaluate the efficacy and safety of anti-PD-1 antibody SHR-1210(Camrelizumab) in combination with a small-molecule multikinase inhibitor Famitinib in subjects with advanced RCC/UC/CC/EC and recurrent OC. chort1: Renal Cell Carcinoma (RCC) chort2: Urothelial Carcinoma(UC) chort3: Ovarian Cancer (OC) chort4: Cervical Cancer (CC) chort5: Endometrial Cancer (EC)

Olaparib Tablets Maintenance Monotherapy Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

This is a prospective, open-label, single arm, multi-centre interventional study to assess the clinical efficacy and safety of olaparib maintenance monotherapy and will be conducted in patients with platinum sensitive relapsed (PSR) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy