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An Exploratory Study on the Use of Ipalotinib (Tislelizumab) Combined With Sunitinib and Olaparib for Neoadjuvant Therapy in HRD-positive Advanced Ovarian Cancer

2026年6月19日 更新者:Bai-Rong Xia
The R0 resection rate in neoadjuvant chemotherapy for advanced ovarian cancer remains below 50%, indicating unmet clinical needs. Tyrosine kinase inhibitors (TKIs) can induce immune microenvironment remodeling and exhibit synergistic effects with immune checkpoint inhibitors. To further evaluate the efficacy and safety of epalolide combined with torvolumab plus sunitinib and olaparib as neoadjuvant therapy in HRD-positive untreated patients with advanced ovarian cancer, a prospective, multicenter, single-arm exploratory study is proposed. This study will enroll 35 untreated HRD-positive advanced ovarian cancer patients who will receive neoadjuvant treatment with epalolide plus torvolumab combined with sunitinib and olaparib. Patients achieving CR/PR/SD after neoadjuvant therapy will undergo intermediate tumor cytoreductive surgery, followed by 6 cycles of adjuvant chemotherapy and 1 year of maintenance therapy with the etoricoxib-drug combination antibody regimen. The primary endpoint is R0 resection rate, aiming to provide valuable insights into neoadjuvant treatment strategies for advanced ovarian cancer patients.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

For patients with advanced ovarian cancer, tumor debulking surgery is a crucial component of treatment. However, due to poor prognosis and high recurrence rates in advanced cases, treatment poses significant challenges. The primary principle of surgical management for advanced ovarian cancer is to achieve maximal tumor resection. The core objective of surgery is to remove all macroscopically visible tumor tissue to minimize postoperative residual disease. Nevertheless, given the complexity of advanced ovarian cancer and individual patient variability, not all patients are suitable candidates for initial tumor debulking surgery. Neoadjuvant chemotherapy combined with intermediate tumor debulking surgery serves as a therapeutic option for patients who cannot achieve satisfactory tumor reduction or are unable to tolerate surgery, and this approach is currently widely employed in clinical practice.

The traditional neoadjuvant treatment regimen for ovarian cancer involves the platinum-paclitaxel dual-drug combination. However, the complete resection rate with pure neoadjuvant chemotherapy remains below 50%, and approximately half of patients fail to achieve complete tumor removal. These patients face the risk of residual tumors postoperatively, which increases the likelihood of disease recurrence, highlighting a significant unmet clinical need. Improving neoadjuvant treatment strategies for ovarian cancer has become a current research focus. Existing studies demonstrate that combining immune checkpoint inhibitors with neoadjuvant chemotherapy can enhance the pathological complete response (pCR) rate in advanced ovarian cancer patients and induce durable clinical responses, suggesting this approach as a promising therapeutic option; however, further validation is required, and the optimal immunotherapy combination strategy requires further exploration.

Apatinib-tolilimumab (hereinafter referred to as the Ato combination antibody) is the world's first dual-functional combination antibody targeting both PD-1 and CTLA-4, capable of simultaneously inhibiting PD-1-and CTLA-4-mediated signaling pathways to exert synergistic antitumor effects with excellent tolerability. In Phase I clinical studies, the Ato combination antibody demonstrated superior safety and tolerability. Among 518 patients with advanced cancer who had failed conventional treatments, only 8.1% experienced grade 3 or higher immune-related adverse events, highlighting its significant safety advantages. In patients with recurrent or metastatic cervical cancer, the pivotal Phase II registration study of the Ato combination antibody achieved remarkable results: an overall response rate (ORR) of 33.8% in second-line systemic therapy and a median progression-free survival (PFS) of 5.4 months. Based on these data, the Ato combination antibody was approved for marketing in China on September 30,2024, indicated for the treatment of recurrent or metastatic cervical cancer patients who had previously failed platinum-based chemotherapy.

PARP inhibitors and antiangiogenic agents can disrupt tumor growth through distinct mechanisms, with their synergistic effects mutually enhancing each other to achieve a 1+1>2 outcome. Multitarget tyrosine kinase inhibitors (TKIs) can induce remodeling of the immune microenvironment and activate the tumor immune response, not only significantly increasing T-cell infiltration into tumors but also upregulating the expression of the immune checkpoint CTLA-4, ultimately enabling tumor cells to evade T-cell attack through immune evasion. CTLA-4 blockade enhances T-cell antitumor activity and effectively reverses the inhibitory immune microenvironment. Sunitinib is a TKI currently used as standard therapy for clear cell renal cell carcinoma (ccRCC) and gastrointestinal stromal tumors (GIST). Studies suggest that sunitinib may play a role in tumor immune monitoring and participate in PD-L1 regulation.

In patients with previously untreated advanced ovarian cancer, the use of neoadjuvant therapy combining TKIs and PARP inhibitors with epalolide and torvocizumab has a solid scientific basis and warrants further investigation. This study innovatively employed sunitinib combined with olaparib for one cycle to induce an immune microenvironment, followed by addition of an immune checkpoint inhibitor, demonstrating synergistic effects. To further evaluate the efficacy and safety of sunitinib and olaparib combined with epalolide and torvocizumab in neoadjuvant treatment for these patients, a prospective, multicenter, single-arm exploratory study is planned to provide valuable insights for developing neoadjuvant treatment regimens for advanced ovarian cancer.

研究类型

介入性

注册 (估计的)

35

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

      • Hefei、中国
        • 招聘中
        • Anhui Cancer Hospital
        • 接触:
          • bairong xia, MD

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

描述

Inclusion Criteria:

  1. Female participants aged ≥18 years and ≤75 years at enrollment;
  2. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma, with histopathological confirmation of high-grade serous carcinoma or endometrioid carcinoma, and FIGO stage (2014 edition) III-IV;
  3. Meeting the neoadjuvant indications for ovarian cancer (preoperative evaluation by a gynecologic oncologist indicates low likelihood of achieving R0 resection with initial debulking surgery, or the patient's physical condition is unsuitable for immediate surgery due to poor tolerance to PDS);
  4. Positive HRD testing result;
  5. Presence of at least one measurable lesion meeting RECIST 1.1 criteria;
  6. Expected survival time ≥12 weeks;
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
  8. Absence of severe hematologic, cardiac, pulmonary, hepatic, renal dysfunction, or immunodeficiency disorders. Within one week prior to the first administration, the functional status of vital organs must meet the following requirements (supportive therapies such as any blood components or cell growth factors are prohibited within 14 days before the first dose):

    1. Complete blood count: HGB ≥ 90 g/L; WBC ≥ 4.0 × 10⁹/L; NEUT ≥ 2.0 × 10⁹/L; PLT ≥ 100 × 10⁹/L;
    2. Blood biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; BUN and Cr ≤ 1.5 × ULN with creatinine clearance ≥ 50 mL/min;
    3. Coagulation function: INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN;
    4. Within 4 weeks prior to the first dose, cardiac ultrasound must demonstrate: left ventricular ejection fraction (LVEF)> 50%;
  9. Pregnancy test results must be negative in patients of childbearing age, with voluntary use of effective and reliable contraceptive measures during the study;
  10. Participants must voluntarily enroll in the study, sign an informed consent form, demonstrate good compliance, and agree to participate in follow-up visits.

Exclusion Criteria:

  1. Ovarian cancer, fallopian tube cancer, primary peritoneal cancer (e.g., germ cell tumors), or ovarian tumors with low malignant potential (e.g., borderline tumors) of non-epithelial origin;
  2. Previous receipt of antitumor therapy, including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy (Note: lymph node dissection or biopsy performed for clinical staging purposes using tissue obtained via puncture biopsy or laparoscopic exploration is permitted);
  3. History of other malignancies within the past 5 years, excluding cured localized tumors (e.g., basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ);
  4. Participation in other drug clinical trials and use of investigational drugs within 4 weeks prior to enrollment;
  5. Administration of live attenuated vaccines within 4 weeks before initial dosing or planned during the study period;
  6. Known history of allergy to any component of this regimen;
  7. Subjects with active infectious diseases;
  8. Subjects with any severe and/or uncontrolled diseases;
  9. Active autoimmune diseases requiring systemic treatment within 2 years prior to study initiation, or autoimmune diseases at risk of recurrence; exceptions include: non-systemically treatable dermatoses (e.g., vitiligo, alopecia, psoriasis, or eczema); hypothyroidism due to autoimmune thyroiditis requiring only stable hormone replacement therapy; well-controlled type 1 diabetes mellitus; and conditions deemed by investigators unlikely to recur without external triggers;
  10. Pregnant or breastfeeding women, or women of childbearing potential with positive baseline pregnancy test results.
  11. According to the investigator's assessment, the patient has a severe comorbid condition that poses significant risks to safety or impedes participation in the study, including but not limited to: severe hypertension uncontrolled by medication (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg), myocardial ischemia or myocardial infarction, severe arrhythmias, congestive heart failure grade ≥2, severe pulmonary dysfunction/disease, severe diabetes mellitus, or active infections;
  12. A documented history of neurological or psychiatric disorders, including epilepsy or dementia;
  13. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
  14. Known history of interstitial lung disease or non-infectious pneumonia;
  15. Diagnosis of immunodeficiency or ongoing systemic glucocorticoid therapy or any other form of immunosuppressive treatment;
  16. Presence of any condition increasing bleeding risk, such as severe hemorrhoids, acute gastritis, or gastric and duodenal ulcers;
  17. History of dysphagia or any gastrointestinal disorder affecting drug absorption;
  18. Any other circumstances deemed inappropriate for study participation by the investigator.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Study Medication Regimen
  1. Preoperative neoadjuvant therapy: Sunitinib: 37.5 mg, qd, orally; discontinuation required for at least 4 weeks prior to surgery; Olaparib: 300 mg, bid, every 3 weeks × 3 cycles; Epalolide and Torvori-mab: infusion of sunitinib and olaparib begins on day 22 of treatment, 5 mg/kg intravenous, every 3 weeks × 2 cycles.
  2. Patients who achieve CR/PR/SD after neoadjuvant therapy shall undergo intermediate tumor cytoreductive surgery; those assessed as PD-positive shall receive treatment for recurrent/metastatic ovarian cancer.
  3. Postoperative adjuvant therapy: 6 cycles of chemotherapy; maintenance therapy with etoposide combination antibody plus olaparib ± sunitinib, with etoposide combination antibody maintenance therapy lasting 1 year.
  1. Preoperative neoadjuvant therapy: Sunitinib: 37.5 mg, qd, orally; discontinuation required for at least 4 weeks prior to surgery; Olaparib: 300 mg, bid, every 3 weeks × 3 cycles; Epalolide and Torvori-mab: infusion of sunitinib and olaparib begins on day 22 of treatment, 5 mg/kg intravenous, every 3 weeks × 2 cycles.
  2. Patients who achieve CR/PR/SD after neoadjuvant therapy shall undergo intermediate tumor cytoreductive surgery; those assessed as PD-positive shall receive treatment for recurrent/metastatic ovarian cancer.
  3. Postoperative adjuvant therapy: 6 cycles of chemotherapy; maintenance therapy with etoposide combination antibody plus olaparib ± sunitinib, with etoposide combination antibody maintenance therapy lasting 1 year.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Total resection rate (R0 resection rate)
大体时间:3-month
All macroscopically visible tumor tissues were surgically removed, and no cancer cells were found at the surgical margins under microscopic examination.
3-month

次要结果测量

结果测量
措施说明
大体时间
Objective Response Rate (ORR)
大体时间:12-month
refers to the proportion of patients whose tumor volume has decreased by 30% and maintained this reduction for more than four weeks, calculated as the sum of complete response (CR) and partial response (PR).
12-month
Disease Control Rate (DCR)
大体时间:12-month
refers to the proportion of all cancer patients receiving a specific treatment who exhibit tumor shrinkage or stabilization, with this condition persisting for a defined period.
12-month
Progression-Free Survival (PFS)
大体时间:12-month
refers to the time from randomization until the first occurrence of disease progression or death from any cause.
12-month
Pathological Complete Response rate (pCR rate)
大体时间:12-month
absence of infiltrating tumor cells upon microscopic examination after resection of the primary tumor;
12-month
Overall Survival (OS)
大体时间:12-month
refers to the time from randomization until death from any cause.
12-month
Adverse Events (AEs)
大体时间:12-month
Collect all adverse events occurring in all subjects from the date of signing the informed consent form until 28 days after discontinuation of medication, including clinical symptoms and abnormalities in vital signs or laboratory tests. Record their clinical manifestations, severity, occurrence time, duration, management measures, and prognosis, and assess their correlation with the investigational drug.
12-month

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

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研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年6月1日

初级完成 (估计的)

2027年12月31日

研究完成 (估计的)

2027年12月31日

研究注册日期

首次提交

2026年6月19日

首先提交符合 QC 标准的

2026年6月19日

首次发布 (实际的)

2026年6月25日

研究记录更新

最后更新发布 (实际的)

2026年6月25日

上次提交的符合 QC 标准的更新

2026年6月19日

最后验证

2026年6月1日

更多信息

与本研究相关的术语

其他研究编号

  • 2025-LLYJ-0153

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

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