A First-in-Human Study of Repeat Dosing With REGN2810, a Monoclonal, Fully Human Antibody to Programmed Death - 1 (PD-1), as Single Therapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 398
- 试验地点
- 47
- 主要终点
- Incidence of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a phase 1, open-label, multicenter, ascending-dose escalation study of cemiplimab, alone and in combination with other anti-cancer therapies in patients with advanced malignancies.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of malignancy with demonstrated progression of a solid tumor (non-lymphoma) with no alternative standard-of-care therapeutic option (certain exceptions may apply).
- •At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment (certain exceptions may apply)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
- •Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway) (certain exceptions may apply)
- •Prior treatment with other immune modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments.
- •Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of progression by imaging for at least 6 weeks prior to the first dose of study treatment, and any neurologic symptoms have returned to baseline), and 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 (certain exceptions may apply).
- •Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
- •The information provided above is not intended to contain all considerations relevant to potential participation in a clinical trial, therefore not all inclusion/ exclusion criteria are listed.
研究组 & 干预措施
Monotherapy Cohort
Cemiplimab will be administered alone
干预措施: Cemiplimab (Drug)
Dual Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy
Doses of cemiplimab will be administered in combination with Cyclophosphamide
Doses of cemiplimab will be administered in combination with Docetaxel
干预措施: Cemiplimab (Drug)
Dual Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy
Doses of cemiplimab will be administered in combination with Cyclophosphamide
Doses of cemiplimab will be administered in combination with Docetaxel
干预措施: Hypofractionated radiotherapy (Radiation)
Dual Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy
Doses of cemiplimab will be administered in combination with Cyclophosphamide
Doses of cemiplimab will be administered in combination with Docetaxel
干预措施: Cyclophosphamide (Drug)
Dual Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy
Doses of cemiplimab will be administered in combination with Cyclophosphamide
Doses of cemiplimab will be administered in combination with Docetaxel
干预措施: Docetaxel (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Cemiplimab (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Hypofractionated radiotherapy (Radiation)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Cyclophosphamide (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Docetaxel (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Carboplatin (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: GM-CSF (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Paclitaxel (Drug)
Triple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus Cyclophosphamide
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF
Doses of cemiplimab will be administered in combination with Carboplatin plus Paclitaxel
Doses of cemiplimab will be administered in combination with Carboplatin plus Pemetrexed
Doses of cemiplimab will be administered in combination with Carboplatin plus Docetaxel
干预措施: Pemetrexed (Drug)
Quadruple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide
干预措施: Cemiplimab (Drug)
Quadruple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide
干预措施: Hypofractionated radiotherapy (Radiation)
Quadruple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Quadruple Combination Cohorts
Doses of cemiplimab will be administered in combination with hypofractionated radiotherapy plus GM-CSF plus Cyclophosphamide
干预措施: GM-CSF (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events (TEAEs)
时间窗: Change from baseline to week 48
Primary safety variables include incidence and severity of TEAEs, abnormal laboratory findings and number of participants with dose limiting toxicities (DLTs)
Incidence of abnormal laboratory findings
时间窗: Change from baseline to week 48
Number of participants with dose limiting toxicities (DLTs)
时间窗: Change from baseline to 28 days after first dose of cemiplimab
次要结局
- Antitumor activity measured by overall survival(Up to 249 weeks)
- Response Evaluation Criteria in Solid Tumors (RECIST) as measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)(Change from baseline to week 48)
- Immune-Related Response Criteria (irRC) applied to RECIST measurements(Change from baseline to week 48)
- Incidence of development of anti-cemiplimab antibodies(Up to week 48)
- Antitumor activity measured by progression-free survival (PFS)(Up to 72 weeks)