Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer: A Phase II, Multicenter, Single-Arm Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- PFS1
研究概览
简要总结
This study is a prospective, multicenter, single-arm, open-label phase II clinical trial.
It is planned to enroll 53 subjects with HER2-expressing (IHC 1+, 2+, or 3+) partially platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (defined as disease recurrence occurring ≥6 months and <12 months after the completion of the last platinum-containing therapy).
The study adopts a two-stage sequential treatment strategy:
Stage 1: All enrolled subjects will receive Trastuzumab Rezetecan (4.8 mg/kg IV, Q3W) combined with Bevacizumab (7.5 mg/kg IV, Q3W). Trastuzumab Rezetecan will be administered for a maximum of 1 year, or until disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria are met, whichever occurs first; Bevacizumab will be continued until disease progression, unacceptable toxicity, or other protocol-defined reasons.
Stage 2: Upon confirmed disease progression in Stage 1, subjects will enter Stage 2 to receive platinum-based chemotherapy (e.g., Carboplatin + Paclitaxel, Carboplatin + Liposomal Doxorubicin, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may replace Carboplatin in cases of intolerance, including but not limited to these regimens, determined by the investigator) until subsequent disease progression or unacceptable toxicity.
The primary objective is to evaluate progression-free survival 1 (PFS1) of SHR-A1811 combined with bevacizumab based on RECIST v1.1. Secondary objectives include objective response rate (ORR), disease control rate (DCR), progression-free survival 2 (PFS2), overall survival (OS), and safety and tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Voluntarily agree to participate in the study, provide written informed consent, demonstrate good compliance, and be able to cooperate with protocol-required follow-up visits.
- •Female patients aged 18 to 75 years old (inclusive, calculated from the date of signing the informed consent form).
- •Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (mucinous carcinoma is excluded).
- •Received 1 to 2 prior lines of systemic therapy and must have received prior PARP inhibitor therapy.
- •Partially platinum-sensitive recurrence, defined as disease recurrence occurring ≥6 months but <12 months after the completion of the last platinum-containing therapy:
- •Neoadjuvant and/or adjuvant therapy are combined and counted as 1 line of therapy;
- •Maintenance therapy does not count as a separate line of therapy;
- •Changes in treatment regimens due to reasons other than disease progression (such as intolerable toxicity) are considered part of the same line of therapy and are not counted separately.
- •Confirmed HER2 expression status: IHC 1+, 2+, or 3+.
- •At least one measurable lesion according to RECIST v1.1 criteria (longest diameter ≥10 mm on spiral CT scan, or short axis ≥15 mm for lymph nodes).
- •ECOG performance status (PS) score: 0 to 1..
- •Expected life expectancy ≥12 weeks.
- •Adequate function of vital organs.
排除标准
- •Central nervous system (CNS) metastasis: Untreated or active CNS metastases. Subjects are eligible if CNS metastases have received adequate local therapy (e.g., surgery or radiotherapy), neurological symptoms have returned to baseline (excluding residual signs or symptoms related to CNS treatment), and clinical stability has been maintained for ≥ 4 weeks prior to the first dose.
- •Second primary malignancy, except for the following: adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma; or other malignancies that have been adequately treated with curative intent and have shown no evidence of recurrence or metastasis for >= 2 years prior to the first dose.
- •Uncontrolled pleural effusion or ascites. Subjects are eligible if therapeutic drainage has been performed and clinical stability has been maintained for at least 2 weeks after drainage.
- •Severe pulmonary disease: History of interstitial lung disease (ILD) or non-infectious pneumonitis (such as radiation pneumonitis) requiring systemic corticosteroid therapy; current or suspected ILD, non-infectious pneumonitis, or other active pulmonary inflammation; or significant pulmonary impairment including severe asthma, severe chronic obstructive pulmonary disease (COPD), or restrictive lung disease within 6 months prior to the first dose.
- •Tuberculosis infection: Active pulmonary tuberculosis infection. Subjects who have received adequate and standard anti-tuberculosis therapy and have discontinued anti-tuberculosis treatment for >= 3 months prior to the first dose are eligible.
- •Uncontrolled cardiovascular disease: Poorly controlled or serious cardiovascular disease, including but not limited to unstable angina, symptomatic congestive heart failure (NYHA Class II-IV), acute myocardial infarction within 6 months prior to the first dose, or unstable arrhythmias requiring clinical intervention within 1 month prior to the first dose.
- •High-risk gastrointestinal indications (perforation/fistula): Gastrointestinal perforation, gastrointestinal fistula, tracheoesophageal fistula, urethral fistula, or abdominal abscess occurring within 3 months prior to the first dose, or judged by the investigator to have a high risk of occurrence in the near future. Subjects who have undergone definitive treatments such as artificial stoma or ureteral stent placement and are evaluated by the investigator as clinically stable are eligible.
- •Active infection: Severe infection occurring within 1 month prior to the first dose; any active infection requiring systemic intravenous antimicrobial therapy; or unexplained fever (> 38.5 deg C) from the screening period up to the first dose.
- •Specific prior drug exposure: Prior treatment with antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, or prior single-agent topoisomerase I inhibitor therapy (such as irinotecan, topotecan).
- •Drug hypersensitivity: Known hypersensitivity to any active ingredient or excipient of Trastuzumab Rezetecan (SHR-A1811), including the antibody, payload SHR169265, and linker; known hypersensitivity to any component of Bevacizumab, or a history of severe hypersensitivity reactions.
- •Other comprehensive risks: Any clinical condition that, in the opinion of the investigator, may increase the risk to the subject, interfere with the interpretation of study results, or preclude compliance with the study protocol.
研究组 & 干预措施
Sequential Treatment Group
Stage 1: SHR-A1811 (4.8 mg/kg, IV) + Bevacizumab (7.5 mg/kg, IV), Q3W, until disease progression or intolerable toxicity. Stage 2: Upon confirmed progression in Stage 1, subjects proceed to receive investigator's choice of platinum-based chemotherapy rechallenge until subsequent progression or intolerable toxicity.
干预措施: Trastuzumab Rezetecan (SHR-A1811) (Drug)
Sequential Treatment Group
Stage 1: SHR-A1811 (4.8 mg/kg, IV) + Bevacizumab (7.5 mg/kg, IV), Q3W, until disease progression or intolerable toxicity. Stage 2: Upon confirmed progression in Stage 1, subjects proceed to receive investigator's choice of platinum-based chemotherapy rechallenge until subsequent progression or intolerable toxicity.
干预措施: Platinum-based chemotherapy (Drug)
Sequential Treatment Group
Stage 1: SHR-A1811 (4.8 mg/kg, IV) + Bevacizumab (7.5 mg/kg, IV), Q3W, until disease progression or intolerable toxicity. Stage 2: Upon confirmed progression in Stage 1, subjects proceed to receive investigator's choice of platinum-based chemotherapy rechallenge until subsequent progression or intolerable toxicity.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
PFS1
时间窗: From the first dose of study treatment up to approximately 36 months.
Progression-Free Survival 1 (PFS1) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Defined as the time from the date of the first dose of study treatment to the date of first documented objective tumor progression or death due to any cause, whichever occurs first.
次要结局
- Objective Response Rate (ORR)(Up to approximately 36 months.)
- Disease Control Rate (DCR)(Up to approximately 36 months.)
- Progression-Free Survival 2 (PFS2)(Up to approximately 36 months.)
- Overall Survival (OS)(Up to approximately 36 months.)
- Safety and Tolerability(From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).)