A Phase II Study of PCSK9 Inhibitor Alirocumab and PD-1 Inhibitor Cemiplimab in Patients With Metastatic, Refractory To Prior Anti PD-1 Non-small Cell Lung Cancer: TOP2201
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Response rate associated with combination of alirocumab and cemiplimab
研究概览
简要总结
PCSK9 mediates immune checkpoint blockade resistance by downregulating tumor cell surface MHC class 1 molecules. This study will evaluate if combining the anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab can generate anti-tumor activity and clinical responses in patients with metastatic lung cancer who have progressed on first line immune checkpoint blockade therapy.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically documented recurrent and/or metastatic non-small cell lung cancer
- •Progression after prior PD-1 directed therapy (as monotherapy or in combination with chemotherapy and/or anti-CTLA4, or anti-VEGF agents) - defined as investigator assessed progression from prior treatment
- •If molecularly altered NSCLC including EGFR, ALK, ROS1, MET exon 14, RET, BRAF, NTRK, progression on prior targeted therapy is required
- •Measurable disease by RECIST 1.1
- •ECOG Performance Status 0 or 1
- •Signed written informed consent
- •Minimum of 4 weeks from any other experimental anti-cancer therapies or prior PD-1 treatment
- •Meet all the laboratory criteria per protocol
排除标准
- •Prior treatment with PCSK9 inhibitors
- •Cardiac issues including MI, uncontrolled arrhythmia, symptomatic angina pectoris, active ischemia, or cardiac failure not controlled by medications.
- •Uncontrolled diabetes mellitus, defined as HbA1c > 10
- •Major surgery less than 4 weeks prior to study enrollment
- •Another malignant condition diagnosed within 3 years of study enrollment
- •Intolerance to prior PD-1/L1 treatment including discontinuation for severe or recurrent severe toxicity (including myocarditis or other myocardiotoxity, encephalitis, colitis, diarrhea, pancreatitis, hypo/hyperthyroidism, hypopituitarism, adrenal insufficiency, rash, autonomic neuropathy, myasthenia gravis, Guillain-Barre, myositis/polymyositis, hepatitis, Type 1 Diabetes, thrombocytopenia) or developed an immune checkpoint blockade related immune adverse event that was refractory to steroids and required additional systemic immunosuppressive medication.
- •Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS)
- •Additional exclusion criterion as per listed in the protocol
研究组 & 干预措施
Alirocumab and Cemiplimab
Combination of anti-PCSK9 antibody alirocumab with the anti-PD-1 antibody cemiplimab
干预措施: Alirocumab and Cemiplimab (Combination Product)
结局指标
主要结局
Response rate associated with combination of alirocumab and cemiplimab
时间窗: Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks per RECIST 1.1
Ascertain the response rate associated with alirocumab and cemiplimab, with 95% confidence intervals. Response rate is defined as the proportion of treated subjects with a complete or partial response per RECIST 1.1 criteria. All patients who receive at least one dose of alirocumab and cemiplimab will be considered for the primary outcome analysis
次要结局
- Progression Free Survival(Day 1 of treatment until the date of first documented progression or date of death, whichever comes first, assessed up to 110 weeks)
- Overall survival(Day 1 of treatment until death or off study due to any other reason whichever comes first, assessed up to 110 weeks)
- Safety and tolerability of the combination regimen(Day 1 of treatment until 30 days post last dose)