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
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 入组人数
- 30
- 主要终点
- The objective response rate of the treatment
概览
简要总结
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.
详细描述
Recurrent and metastatic cervical, vulvar, and vaginal cancers represent a significant clinical challenge, with limited treatment options and poor prognosis for patients who have failed standard therapies. These malignancies are often driven by persistent human papillomavirus (HPV) infection, leading to immunosuppression and tumor immune evasion. While immune checkpoint inhibitors, such as anti-PD-1 antibodies, have shown some efficacy, response rates remain suboptimal, highlighting the need for more effective combination strategies.
Becotatug vedotin is an antibody-drug conjugate (ADC) that selectively delivers a potent cytotoxic payload to tumor cells expressing specific antigens, thereby inducing targeted cell death. Zimberelimab is a monoclonal antibody targeting the PD-1 checkpoint receptor, which functions to reactivate the body's immune system to recognize and attack cancer cells. The combination of these two agents is hypothesized to exert a synergistic anti-tumor effect, by directly eliminating tumor cells while simultaneously overcoming immunosuppression in the tumor microenvironment.
This trial will evaluate the safety, tolerability, and preliminary efficacy of this novel combination regimen.
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
- •A subject must meet all of the following criteria to be eligible for enrollment:
- •The subject has a full understanding of the study, voluntarily agrees to participate, and signs the Informed Consent Form (ICF).
- •Female, aged 18 to 75 years (inclusive).
- •Life expectancy ≥ 3 months, as assessed by the investigator.
- •Histologically confirmed squamous cell carcinoma of the cervix, vagina, or vulva.
- •Have received at least one line of standard therapy, which must have included platinum-based chemotherapy and an immunotherapy agent; prior lines of therapy ≤
- •ECOG performance status of 0 or
- •Presence of at least one measurable target lesion according to the RECIST 1.1 criteria.
- •Adequate bone marrow function: absolute neutrophil count ≥ 1.5 × 10⁹/L, platelets ≥ 90 × 10⁹/L, hemoglobin ≥ 90 g/L.
- •Adequate hepatic and renal function: serum creatinine ≤ 1.5 × upper limit of normal (ULN); AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN for subjects with liver metastases); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for subjects with liver metastases).
排除标准
- •A subject will be ineligible for study enrollment if they meet any of the following criteria:
- •Known hypersensitivity or allergic reaction to any study drug or its components.
- •Use of a strong CYP3A4 inducer (e.g., anticonvulsants \[phenytoin, phenobarbital, carbamazepine\], rifampicin, rifabutin, St. John's Wort) within 2 weeks prior to the first dose of study medication; or use of a strong CYP3A4 inhibitor (e.g., grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or a strong UGT1A1 inhibitor (e.g., atazanavir, gemfibrozil, indinavir) within 1 week prior to the first dose.
- •Known central nervous system (CNS) metastases, meningeal metastases, spinal cord metastases or spinal cord compression.
- •Currently having uncontrolled systemic diseases (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus, etc.), or psychiatric disorders/social conditions that would limit the subject's ability to comply with study requirements or provide written informed consent.
- •Radiologically confirmed intestinal obstruction; or a medical history of the following diseases: inflammatory bowel disease, extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis.
- •Active hepatitis B or hepatitis C infection (hepatitis B surface antigen positive with hepatitis B virus DNA \> 1 × 10³ copies/mL; hepatitis C virus RNA \> 1 × 10³ copies/mL).
- •Human immunodeficiency virus (HIV) infection (positive HIV antibody test).
- •Major surgery or severe trauma within 30 days prior to the first dose, or planned major surgery within 30 days after the first dose (as determined by the investigator).
- •Pregnant or breastfeeding women; or women of childbearing potential who refuse to adopt effective contraceptive measures.
研究组 & 干预措施
Becotatug Vedotin in combination with Zimberelimab
Subjects who are enrolled in the study and pass the investigator's screening will receive treatment according to the following regimen:
Becotatug Vedotin 2.0 mg/kg, administered intravenously on Day 1 of each cycle Zimberelimab 240 mg, administered intravenously on Day 1 of each cycle Each treatment cycle is 3 weeks. Treatment will continue until the first occurrence of any of the following events: disease progression, unacceptable toxicity, completion of 12 months of treatment, initiation of new anti-cancer therapy, withdrawal of informed consent, loss to follow-up, death, or other circumstances that the investigator deems necessitate treatment discontinuation.
干预措施: Becotatug Vedotin in combination with Zimberelimab (Drug)
结局指标
主要结局
The objective response rate of the treatment
时间窗: Up to approximately 36 months
The objective response rate of the treatment
次要结局
- duration of response(Up to approximately 36 months)
- progression free survival(Up to approximately 36 months)
- Overall Survival(Up to approximately 36 months)
研究者
Guiling Li
professor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology