IN10018 Plus Nab-Paclitaxel and Cadonilimab for Metastatic, Recurrent, or Persistent Gastric-Type Adenocarcinoma of the Cervix: A Multicenter, Single-Arm, Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Gastric-type adenocarcinoma of the cervix is the most commonly diagnosed HPV-independent subtype of cervical cancer, characterized by a poor prognosis and limited responsiveness to existing therapies. Therefore, the exploration of new treatment modalities is critically important. This is an open-label, single-arm, multi-center clinical trial to evaluate the efficacy and safety of IN10018 plus nab-paclitaxel and cadonilimab in the treatment of adult women with metastatic, recurrent, or persistent gastric-type adenocarcinoma of the cervix.
详细描述
Subjects will receive IN10018 at a dose of 100 mg orally once daily, in combination with nab-paclitaxel at 260 mg/m² and cadonilimab at 10 mg/kg, both administered via intravenous infusion on Day 1 of each 3-week cycle. Tumor assessments will be conducted every 2 cycles throughout the treatment period. If the therapy proves effective, chemotherapy will continue for up to 6 cycles. Upon completion of chemotherapy, maintenance therapy with cadonilimab and IN10018 will begin and continue until either disease progression or the emergence of intolerable toxicity.
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
- •Females 18-75 years of age.
- •Patients must have metastatic, recurrent or persistent gastric-type adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
- •Patients must have had at least one prior systemic chemotherapeutic regimen for metastatic, recurrent or persistent carcinoma of the cervix. (Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of metastatic, recurrent or persistent carcinoma of the cervix, adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT).
- •Patients must have measurable disease per REClST 1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis.
- •Eastern Cooperative Oncology Group score 0-
- •Life expectancy exceeds 3 months.
- •AEs due to previous treatments should be resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy are eligible.
- •NEU ≥ 1.5*10^9 /L, Platelet ≥ 75×10^9 /L, Hemoglobin ≥ 90 g/L; Serum creatinine ≤ 1.5 times the upper limit of normal (ULN).; Urinary protein < 2+ or 24h urinary protein quantity < 1.0 g; AST and ALT ≤ 2.5 times ULN; Total bilirubin ≤ 1.5 times ULN; Albumin levels ≥ 28 g/L; Coagulation function: Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 times the ULN.
- •Female participants must test negative for HCG in urine or blood, except in cases of menopause or prior hysterectomy. Female patients of childbearing potential and their partners must use effective contraception during the study and for 6 months after the final dose of the study drug.
- •Willing to participate in this study, and sign the informed consent.
排除标准
- •Patients with cervical cancer histologically diagnosed as squamous cell carcinoma, usual-type adenocarcinoma, clear cell carcinoma, adenosquamous carcinoma, small cell carcinoma, or any non-gastric-type adenocarcinoma.
- •Participate in other drug clinical trials at the same time.
- •Known hypersensitivity to any component of the IN10018 formulation or to cadonilimab.
- •Patients with active autoimmune disease or a history of autoimmune disorders.
- •Patients with concomitant conditions requiring immunosuppressive medications or systemic or absorbable local corticosteroids at immunosuppressive doses. The use of prednisone >10 mg/day or an equivalent dose is prohibited within 2 weeks prior to the first administration of the investigational drug.
- •HIV infection or a positive test for acquired immunodeficiency syndrome (AIDS).
- •Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Necrotic lesions identified within 4 weeks prior to enrollment, where there is a high risk of major bleeding as determined by the investigator.
- •Severe infections occurring within 4 weeks prior to the first dose of study treatment.
- •Known active tuberculosis (TB) or suspicion of active TB.
- •Untreated chronic hepatitis B infection or hepatitis B virus (HBV) carriers with HBV DNA levels exceeding 1000 IU/mL, or patients with active hepatitis C infection.
- •Patients with known leptomeningeal disease, spinal cord compression, or active brain metastases.
- •Uncontrolled severe medical conditions that, in the investigator's judgment, would interfere with the patient's ability to receive study treatment, including but not limited to severe cardiovascular disease, cerebrovascular disease, uncontrolled diabetes, or uncontrolled infections.
- •Receipt of a live vaccine within 4 weeks prior to the first dose of study treatment. Note: Inactivated seasonal influenza vaccines are permitted.
- •Pregnant or breastfeeding female patients, or female patients of childbearing potential who refuse to use effective contraception.
- •Patients with symptomatic or unstable third-space fluid accumulations (e.g., pleural effusion, ascites, pericardial effusion) requiring repeated drainage.
- •Patients with a prior genetic test report indicating mutations associated with hyperprogression under immunotherapy, such as MDM2/4 amplification or EGFR mutations.
- •Not eligible for the study judged by researchers.
研究组 & 干预措施
Study group
IN10018 is administered orally at a dose of 100 mg once daily; cadonilimab is given at a dose of 10 mg/kg via intravenous infusion on Day 1 of each cycle, every 3 weeks; and nab-paclitaxel is administered at a dose of 260 mg/m² via intravenous infusion on Day 1 of each cycle, also every 3 weeks. Patients will undergo a maximum of 6 cycles of this combination chemotherapy. Following this regimen, maintenance therapy will consist of a combination of cadonilimab and IN10018.
干预措施: IN10018 (Drug)
Study group
IN10018 is administered orally at a dose of 100 mg once daily; cadonilimab is given at a dose of 10 mg/kg via intravenous infusion on Day 1 of each cycle, every 3 weeks; and nab-paclitaxel is administered at a dose of 260 mg/m² via intravenous infusion on Day 1 of each cycle, also every 3 weeks. Patients will undergo a maximum of 6 cycles of this combination chemotherapy. Following this regimen, maintenance therapy will consist of a combination of cadonilimab and IN10018.
干预措施: Nab-paclitaxel (Drug)
Study group
IN10018 is administered orally at a dose of 100 mg once daily; cadonilimab is given at a dose of 10 mg/kg via intravenous infusion on Day 1 of each cycle, every 3 weeks; and nab-paclitaxel is administered at a dose of 260 mg/m² via intravenous infusion on Day 1 of each cycle, also every 3 weeks. Patients will undergo a maximum of 6 cycles of this combination chemotherapy. Following this regimen, maintenance therapy will consist of a combination of cadonilimab and IN10018.
干预措施: Cadonilimab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Every 6 weeks from the time of the first dose of the study drug until the completion of treatment, lasting approximately 18 weeks.
ORR is defined as the percentage of the participants in the ITT population who have a complete response (CR) or partial response (PR). The ORR will be assessed by a blind independent central reviewer per RECIST 1.1
次要结局
- Progression-free survival (PFS)(2 years)
- Disease Control Rate (DCR)(Every 6 weeks from the time of the first dose of the study drug until the completion of treatment, lasting approximately 18 weeks.)