A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients With Advanced Cutaneous Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 432
- 试验地点
- 78
- 主要终点
- Overall Response Rate (ORR) by Independent Central Review
研究概览
简要总结
The goals of this study are to evaluate the clinical benefit and safety of cemiplimab in participants with metastatic (nodal or distant) Cutaneous Squamous Cell Carcinoma (CSCC), or unresectable locally advanced CSCC.
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
- •At least 1 measurable lesion
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Adequate bone marrow function
- •Adequate renal function
- •Adequate hepatic function
- •Archived or newly obtained tumor material
- •Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6)
- •Surgical or radiological treatment of lesions contraindicated
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
- •Prior treatment with an agent that blocks the PD-1/PD-L1pathway
- •Prior treatment with a BRAF inhibitor
- •Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-
- •Untreated brain metastasis(es) that may be considered active
- •Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
- •Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus
- •History of non-infectious pneumonitis within the last 5 years
- •Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
- •Known allergy to doxycycline or tetracycline
- •Patients with a history of solid organ transplant
- •Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Group 1 (Participants With mCSCC): Cemiplimab 3 mg/kg Q2W
Participants received cemiplimab 3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks (Q2W) during each 8-week treatment cycle, for up to 96 weeks (12 cycles).
干预措施: cemiplimab (Drug)
Group 2 (Participants With laCSCC): Cemiplimab 3 mg/kg Q2W
Participants received cemiplimab 3 mg/kg IV Q2W during each 8-week treatment cycle, for up to 96 weeks (12 cycles).
干预措施: cemiplimab (Drug)
Group 3 (Participants With mCSCC): Cemiplimab 350 mg Q3W
Participants received cemiplimab 350 mg IV every 3 weeks (Q3W) during each 9-week treatment cycle, for up to 54 weeks (6 cycles).
干预措施: cemiplimab (Drug)
Group 4 (Participants With mCSCC and laCSCC): Cemiplimab 600 mg Q4W
Participants received cemiplimab 600 mg IV every 4 weeks (Q4W) during each 8-week treatment cycle, for up to 48 weeks (6 cycles).
干预措施: cemiplimab (Drug)
Group 5 (Participants With mCSCC and laCSCC): Cemiplimab SC + 350 mg Q3W
Participants received a single subcutaneous (SC) dose of cemiplimab followed by cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 54 weeks (6 cycles).
干预措施: cemiplimab (Drug)
Group 6 (Participants With mCSCC and laCSCC): Cemiplimab 350 mg Q3W
Participants received cemiplimab 350 mg IV Q3W during each 9-week treatment cycle, for up to 108 weeks (12 cycles).
干预措施: cemiplimab (Drug)
结局指标
主要结局
Overall Response Rate (ORR) by Independent Central Review
时间窗: Up to 108 weeks
ORR was defined as percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). For participants with metastatic disease, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) \<1 (centimeter (cm). -PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
次要结局
- ORR by Investigator Assessment(Up to 108 weeks)
- Duration of Response (DOR) by Independent Central Review(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- DOR by Investigator Assessment(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- Progression-Free Survival (PFS) by Independent Central Review(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- PFS by Investigator Assessment(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- Overall Survival (OS)(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- Complete Response (CR) Rate by Independent Central Review(Up to 108 weeks)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Score(Baseline, Up to Cycle 12 Day 1 (Week 89))
- DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays(Up to approximately 65 months (treatment period + follow-up including survival follow-up))
- Number of Participants With Any Treatment Emergent Adverse Event (TEAE)(Up to 108 weeks plus 105 days (5 half-lives))
- Peak Concentration (Cmax) of Cemiplimab(Up to approximately 43 months)
- Trough Concentration (Ctrough) of Cemiplimab(Up to approximately 43 months)
- Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies(Up to approximately 43 months)
- ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays(Up to 108 weeks)
- PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays(Up to approximately 65 months (treatment period + follow-up including survival follow-up))