A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Cemiplimab (Anti-PD-1) and Other Agents in Japanese Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 146
- 试验地点
- 20
- 主要终点
- Incidence and severity of TEAEs in patients treated with cemiplimab in combination with other agents
研究概览
简要总结
Part 2 Cohorts A and C This study is being conducted to test the safety and pharmacokinetics of cemiplimab in patients with lung cancer. The study is also being conducted to test if cemiplimab, alone or in combination, can reduce the size of your tumor by helping the immune system destroy the tumor.
Part 2 Cohorts D and E This study is being conducted to test the safety and pharmacokinetics of fianlimab and cemiplimab in patients with lung cancer. The study is also being conducted to test if fianlimab and cemiplimab, with or without chemotherapy, can reduce the size of your tumor by helping the immune system destroy the tumor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease types under study:
- •Part 1: Histologically or cytologically confirmed diagnosis of malignancy with no alternative standard-of-care therapeutic option
- •Part 2: Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC or stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC.
- •Patients in Part 2 NSCLC cohorts must have available archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated.
- •ECOG (Eastern Cooperative Oncology Group) PS (Performance status) ≤1 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature [eg, light housework or office work]). Note: Patients with ECOG PS >1 are ineligible.
- •Patients must have been born in Japan, and their biological parents and grandparents must all have been of Japanese origin
- •Willing and able to comply with clinic visits and study-related procedures
- •For Part 2, Cohorts D and E: Available tissue for retrospective testing using assay performed by a central laboratory, as specified in the study manual.
排除标准
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires treatment with systemic immunosuppressive treatments, which may suggest risk for Immune-mediated adverse event (imAE)s. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement or psoriasis that does not require systemic treatment.
- •Untreated brain metastasis (es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable, there is no evidence of new or enlarging brain metastases, and the patient does not require any systemic corticosteroids for management of brain metastases within 4 weeks prior to the first dose of cemiplimab.
- •Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab.
- •Any positive test (ribonucleic acid (RNA) or Deoxyribonucleic acid (DNA) by polymerase chain reaction) for hepatitis B, hepatitis C, or human immunodeficiency virus indicating uncontrolled active or chronic infection.
- •History of pneumonitis or interstitial lung disease
- •Surgery within 1 month of first dose and radiation therapy within 2 weeks of first dose
- •Completed palliative radiation therapy within the prior 2 weeks or has not recovered from any medically significant radiation-related Adverse Event (AE)
- •Patients that have never smoked, defined as smoking ≤100 cigarettes in a lifetime (Part 2)
- •Patients with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS1 fusions (Part 2)
- •Note: Other protocol defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Cemiplimab
Part 1
干预措施: Cemiplimab (Drug)
Cohort A
Part 2
干预措施: Cemiplimab (Drug)
Cohort B
Part 2
干预措施: Cemiplimab (Drug)
Cohort B
Part 2
干预措施: Ipilimumab (Drug)
Cohort B
Part 2
干预措施: Platinum-doublet chemotherapy (Drug)
Cohort B
Part 2
干预措施: Gemcitabine (Drug)
Cohort B
Part 2
干预措施: Pemetrexed (Drug)
Cohort B
Part 2
干预措施: Paclitaxel (Drug)
Cohort C
Part 2
干预措施: Cemiplimab (Drug)
Cohort C
Part 2
干预措施: Platinum-doublet chemotherapy (Drug)
Cohort C
Part 2
干预措施: Pemetrexed (Drug)
Cohort C
Part 2
干预措施: Paclitaxel (Drug)
Cohort D
Part 2
干预措施: Cemiplimab (Drug)
Cohort D
Part 2
干预措施: Fianlimab (Drug)
Cohort E
Part 2
干预措施: Cemiplimab (Drug)
Cohort E
Part 2
干预措施: Platinum-doublet chemotherapy (Drug)
Cohort E
Part 2
干预措施: Pemetrexed (Drug)
Cohort E
Part 2
干预措施: Paclitaxel (Drug)
Cohort E
Part 2
干预措施: Fianlimab (Drug)
结局指标
主要结局
Incidence and severity of TEAEs in patients treated with cemiplimab in combination with other agents
时间窗: Up to 136 weeks
Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab without chemotherapy
时间窗: Up to 136 weeks
PK of cemiplimab: tmax
时间窗: Up to 136 weeks
Time to Cmax
Incidence and severity of treatment-emergent adverse events (TEAEs) in patients treated with cemiplimab as monotherapy
时间窗: Up to 136 weeks
Incidence and severity of TEAEs in patients treated with fianlimab in combination with cemiplimab with chemotherapy
时间窗: Up to 136 weeks
PK of cemiplimab: Cmax
时间窗: Up to 136 weeks
Peak serum concentration
PK of cemiplimab: Ctrough
时间窗: Up to 136 weeks
Drug concentration in serum at the end of a dosing interval
PK of cemiplimab: Area under the drug concentration-time curve in serum (AUC3w)
时间窗: Up to 136 weeks
AUC over a 3-week dosing interval
PK of cemiplimab: t½ estimated over a 3-week dosing interval
时间窗: Up to 136 weeks
Observed terminal half-life
次要结局
- Objective Response Rate (ORR)(Up to 135 weeks)
- Duration of Response (DOR)(Up to 136 weeks)
- Immunogenicity against cemiplimab and fianlimab(Up to 136 weeks)