Surgery With ICBs in BRCAwt, CD8+ TILs, 1st Relapsed Ovarian Cancer: A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Progression-free survival in CF arm
研究概览
简要总结
This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with anti-PD1/CTLA-4 bispecifics therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC).
详细描述
The immune phenotype of patients with relapsed ovarian cancer may correlate with their response to immunotherapy. This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with anti-PD1/CTLA-4 bispecifics therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC). PD-L1 expression and CD8+ tumor-infiltrating T cell count (CD8+ TILs count) were evaluated as biomarkers using archived or fresh tumor tissue samples in patients with BRCA1/2 wild type.
This study would be proceeded in two phases. The phase 1b single-arm study aimed to evaluate the efficacy of Iparomlimab/tuvonralimab in the treatment of BRCA wild type, PD-L1-positive, CD8+ TILs-positive, patients with PSROC. The patent-centric phase II study with three arms aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with Iparomlimab/tuvonralimab in these patients. In arm 1 and 2, patients received secondary cytoreduction followed by platinum-based chemotherapy in combination with Iparomlimab/tuvonralimab. In arm 3, patients received physician's therapy of choice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Arm 1 (criteria-fulfilled, CF)
- •Age at recurrence ≥ 18 years, <80 years.
- •Patients with platinum-sensitive, first relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer (EOC, PPC, FTC), which is defined as those with treatment -free interval of 6 months or more.
- •If the patient had previous PARPi maintenance therapy, disease progression should occurring at lease 3 months after the prior PARPi withdrawal.
- •BRCA1/2 wild type (both germline and somatic)
- •Homologous Recombination Deficiency (HRD) is available
- •Patients must provide archived or fresh tumor tissue samples for biomarker detection.
- •PD-L1 positive (if either at least 1% of assessed tumour cells expressed membranous PD-L1, at least 5% of immune cells within the tumour area expressed PD-L1, or both) and number of intraepithelial CD8+ tumor-infiltrating lymphocytes (TILs) per high-powered field ≥
- •Assessed by the experienced surgeons, complete resection of all recurrent disease is possible (predicted by iMODEL score or by PET/CT).
- •ECOG performance status of 0 to 2
- •Adequate bone marrow, liver, and renal function to receive combined immunotherapy
- •Written informed consent
- •Arm 2 (compassionate use, CU), Similar to cohort 1, except for:
- •If the patient had previous PARPi maintenance therapy, disease progression should occurring within 3 months after the prior PARPi withdrawal or during the PARPi maintenance therapy.
- •PD-L1 positive or number of intraepithelial CD8+ TILs per high-powered field ≥
- •Arm 3 (real word) Patients who meet the inclusion criteria but refuse to participate in the phase II CF and CU cohorts.
排除标准
- •Patients with borderline, low-grade tumors, clear cell carcinoma, as well as non-epithelial tumors.
- •Patients with platinum-resistant or refractory diseases.
- •Lack of tumor samples (archived and/or recently obtained) for biomarker detection.
- •Previous administration of immunotherapy
- •Patients have been vaccinated with the live vaccine or received anti-tumor treatment within 4 weeks before the first administration.
- •Synchronous or metachronous (within 5 years) malignancy, symptomatic or uncontrolled visceral metastases that require simultaneous treatment, other than carcinoma in situ or breast cancer (without any signs of relapse or activity).
- •Patients with parenchymal metastases and life-threatening complications in short term.
- •Any other concurrent medical conditions contraindicating surgery, chemotherapy, or immunotherapy that could compromise the adherence to the protocol.
- •Patients are known to be allergic to the active ingredients or excipients of Sintilimab.
- •HRD status is not available.
- •Any medication induced considerable risk of surgery, e.g. estimated bleeding due to oral anticoagulating agents or bevacizumab.
- •Patients for interval-debulking, or for second-look surgery, or palliative surgery planned.
- •Impossible to assess the resectability of recurrent disease or evaluate the score. Radiological signs suggesting complete resection is impossible.
研究组 & 干预措施
criteria-fulfilled arm
Patients who meet the inclusion and exclusion criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.
干预措施: surgery/chemotherapy (Procedure)
criteria-fulfilled arm
Patients who meet the inclusion and exclusion criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.
干预措施: Iparomlimab/Tuvonralimab (Drug)
compassionate use arm
Patients who are enrolled under expanded eligibility criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.
干预措施: surgery/chemotherapy (Procedure)
compassionate use arm
Patients who are enrolled under expanded eligibility criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.
干预措施: Iparomlimab/Tuvonralimab (Drug)
结局指标
主要结局
Progression-free survival in CF arm
时间窗: Up to 3 years
The time from entry into the study to the diagnosis of the first progression or recurrence or death in CF arm, whichever occurs first
3-years Overall Survival Rate in CF arm
时间窗: Up to 3 years
The proportion of patients without death at 3 years after entry into the study in CF arm
次要结局
- Overall survival in CF arm(Up to 3 years)
- TFST in CF arm(Up to 3 years)
- TSST in CF arm(Up to 3 years)
- Post-operative complications in CF and CU arms(Up to 1 months)
- Quality of life assessments in CF arm using EORTC QLQ-C30(Up to 3 years)
- Quality of life assessments in CF arm using FACT-O(Up to 3 years)