The Efficacy and Safety of Sacituzumab in Patients With Ovarian Clear Cell Carcinoma After the Progression of Immunotherapy: A Prospective Real-world Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 22
- 主要终点
- Objective response rate
研究概览
简要总结
Ovarian clear cell carcinoma (OCCC) is a relatively rare but highly malignant epithelial ovarian cancer, accounting for 5%-10% of all ovarian cancers. The incidence of this tumor has significant racial disparity, with the highest incidence in Asians, accounting for 25% of ovarian cancer patients, while in European and American ovarian cancer patients, it only accounts for 4.8%. Due to the unique biological behavior of OCCC, it responds poorly to traditional platinum-based chemotherapy regimens, and the prognosis of patients with advanced and recurrent disease is extremely poor.
OCCC has low sensitivity to platinum-based chemotherapy, especially in recurrent or persistent disease, and the objective response rate (ORR) of chemotherapy is usually less than 10%. Although immunotherapy has shown good results in OCCC, 60% of patients still cannot shrink their tumors after using combination regimens, and 50% of patients will still progress after 6.9 months of treatment. The question of how to treat OCCC after progression on immunotherapy remains a pressing issue. Sacituzumab (SKB264) is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (Trop-2) monoclonal antibody conjugated to T030. In the KL264-I-01 study (which included patients with OCCC) in patients with recurrent ovarian cancer, single-agent Sacituzumab achieved an objective response rate of 40%, superior to conventional chemotherapy, with manageable toxicity. OCCC patients who progress on immunotherapy face a dilemma of limited treatment options. Based on this current situation and the potential activity of Sacituzumab the investigators propose Sacituzumab as an option for patients with OCCC after immunotherapy progression.
详细描述
Ovarian clear cell carcinoma (OCCC) is a relatively rare but highly malignant epithelial ovarian cancer, accounting for 5%-10% of all ovarian cancers. The incidence of this tumor has significant racial disparity, with the highest incidence in Asians, accounting for 25% of ovarian cancer patients, while in European and American ovarian cancer patients, it only accounts for 4.8%. Due to the unique biological behavior of OCCC, it responds poorly to traditional platinum-based chemotherapy regimens, and the prognosis of patients with advanced and recurrent disease is extremely poor.
OCCC has low sensitivity to platinum-based chemotherapy, especially in recurrent or persistent disease, and the objective response rate (ORR) of chemotherapy is usually less than 10%. The OCCC tumor microenvironment indicates that OCCC is a "hot tumor," suggesting that patients may benefit from immunotherapy. This benefit has been confirmed in clinical studies. Although immunotherapy has shown good results in OCCC, 60% of patients still cannot shrink their tumors after using combination regimens, and 50% of patients will still progress after 6.9 months of treatment. The question of how to treat OCCC after progression on immunotherapy remains a pressing issue. Sacituzumab (SKB264) is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (Trop-2) monoclonal antibody conjugated to T030. In the KL264-I-01 study (which included patients with OCCC) in patients with recurrent ovarian cancer, single-agent Sacituzumab achieved an objective response rate of 40%, superior to conventional chemotherapy, with manageable toxicity. OCCC patients who progress on immunotherapy face a dilemma of limited treatment options. Based on this current situation and the potential activity of Sacituzumab the investigators propose Sacituzumab as an option for patients with OCCC after immunotherapy progression.
The investigators plan to conduct a prospective, real-world clinical study to enroll patients with OCCC who have developed resistance to immunotherapy and receive Sacituzumab (5 mg/kg intravenous infusion, 2 weeks of treatment). The investigators will prospectively observe and collect treatment responses, efficacy data, and safety events, and compare the efficacy with that of a historical cohort of immunotherapy-resistant patients who received traditional chemotherapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically diagnosed ovarian clear cell carcinoma
- •Patients who have progressed on imaging assessment after receiving immunotherapy, including anti-PD-1, PD-L1, and PD-1/PD-L1+CTLA4, and subsequently received Sacituzumab.
- •At least one measurable lesion as assessed by RECIST, version 1.
- •Life expectancy ≥ 12 months.
- •Normal renal an liver function, no myelosuppression.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score (PS score) 0-
- •Participants must have recovered from all toxicities resulting from previous treatment (recovery to < grade 1 or protocol-specified inclusion criteria, based on a CTCAE 5.0 assessment), excluding alopecia.
- •Participants must be willing to participate in the study, be compliant, sign the informed consent form, and be able to adhere to protocol-specified visits and procedures.
排除标准
- •Receipt of more than two lines of therapy after progression on immunotherapy.
- •Previous use of irinotecan or ADCs containing topoisomerase I inhibitors.
- •Presence or history of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment
- •Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or a history of corneal disease that prevents delayed corneal healing.
- •Concomitant incomplete or complete intestinal obstruction, intestinal fistula of any grade, hydronephrosis that cannot be resolved with a ureteral stent, inflammatory bowel disease or brain metastases.
- •Organ transplant recipient.
- •≥ Grade 3 venous embolism
- •Active infectious disease of any grade, including tuberculosis.
- •Previous history of pelvic or abdominal radiation therapy to any site.
- •Concurrent with other types of malignant tumors.
- •Mental status abnormalities.
- •Pregnant or lactating women; or patients of childbearing potential (male or female) who are unable to use effective medical contraception during the study period and for 6 months after the end of dosing.
- •Any other condition deemed inappropriate for participation in this study by the investigator.
结局指标
主要结局
Objective response rate
时间窗: 2 years
The proportion of patients whose tumor volume was reduced by more than 30% and maintained for 4 weeks
次要结局
- Adverse event(2 years)
- Overall survival(From enrollment to 2 years after treatment completion)
- Progression free survival(From enrollment to 2 years after treatment completion)
研究者
Jing Li
professor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University