A Single-Arm, Multicenter, Open-Label Phase Ib/II Clinical Study Exploring the Efficacy and Safety of Iparomlimab and Tuvonralimab Injection in Combination With Chemotherapy for the Treatment of Malignant Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 55
- 主要终点
- ORR
研究概览
简要总结
This clinical trial aims to investigate the effectiveness and safety of a new treatment combination-Iparomlimab and Tuvonralimab (QL1706, a dual-function antibody targeting PD-1 and CTLA-4) combined with chemotherapy-for patients with malignant mesothelioma (MM). MM is a rare and aggressive cancer often linked to asbestos exposure. Current treatments have limited success, and this study seeks to explore a potentially more effective and safer option.
Study Design:
Phase Ib (Safety Phase): 6 patients will receive the combination therapy to assess safety. If no major safety issues arise, the study will proceed to Phase II.
Phase II (Efficacy Phase): 49 patients will be enrolled to evaluate treatment effectiveness. The study includes two groups for first-line treatment and second-line treatment.
详细描述
Study Rationale Malignant mesothelioma (MM) is a rare and aggressive cancer primarily associated with asbestos exposure. Despite advances in treatment, the prognosis remains poor, with a median overall survival (OS) of approximately 12-18 months for advanced disease. Current standard therapies include platinum-based chemotherapy combined with pemetrexed, immune checkpoint inhibitors (ICIs) such as nivolumab plus ipilimumab, or pembrolizumab with chemotherapy. However, these treatments have limitations, including significant toxicity (e.g., immune-related adverse events, irAEs) and modest survival benefits in certain populations.
The iparomlimab and tuvonralimab (QL1706) combination is a novel bispecific antibody therapy targeting PD-1 and CTLA-4, designed to enhance anti-tumor immune responses while minimizing toxicity. Preclinical and early clinical data suggest this dual checkpoint blockade may offer comparable efficacy to existing ICI combinations but with an improved safety profile. Given the unmet need for effective and tolerable therapies in MM, this study evaluates the clinical potential of iparomlimab and tuvonralimab combined with chemotherapy in Chinese patients.
Study Design
This is a single-arm, multicenter, open-label Ib/II trial with two sequential phases:
Phase Ib (Safety Run-In, n=6):
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
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must provide informed consent prior to initiating any study-specific procedures.
- •Male or female subjects aged ≥18 and ≤75 years.
- •Histologically/cytologically confirmed malignant mesothelioma (MM), including malignant pleural mesothelioma (PM) and malignant peritoneal mesothelioma (PeM).
- •Subjects with MM unsuitable for radical resection and/or radiotherapy per AJCC 8th Edition.
- •Subjects who received neoadjuvant/adjuvant chemotherapy for radical surgery completed >6 months prior to current recurrent disease diagnosis, not counted in subsequent treatment lines.
- •Prior systemic anti-tumor therapy requirements:
- •Safety run-in phase: ≥1 prior anti-tumor therapy line (maximum 3 lines)
- •Phase II first-line cohort: No prior systemic anti-tumor therapy
- •Phase II second-line cohort: Only 1 prior systemic anti-tumor therapy line
- •ECOG performance status 0-
- •Investigator-assessed life expectancy >3 months.
- •Adequate hematological parameters.
排除标准
- •Prior CTLA-4 inhibitors prohibited; prior PD-1/PD-L1 allowed unless discontinued for immune toxicity
- •Immunomodulators within 14 days (e.g., thymosin, interleukin-2, interferon)
- •Significant cardiovascular history within 6 months
研究组 & 干预措施
Arm: Iparomlimab and Tuvonralimab Combined with Chemotherapy
Patients will receive Iparomlimab and Tuvonralimab (5 mg/kg) plus chemotherapy (pemetrexed and platinum drugs) every 3 weeks for 4-6 cycles, followed by maintenance therapy with Iparomlimab and Tuvonralimab for up to 2 years.
干预措施: iparomlimab and tuvonralimab (Dual PD-1/CTLA-4 blockade) + chemotherapy (Drug)
结局指标
主要结局
ORR
时间窗: From enrollment to the end of treatment at 8 weeks
Objective Response Rate，Proportion of participants achieving complete response (CR) or partial response (PR) per modified RECIST 1.1 for mesothelioma
次要结局
未报告次要终点
研究者
Puyuan Xing
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
National Cancer Center, China