A Randomized, Controlled, Open-Label, Phase 2 Study of Cemiplimab as a Single Agent and in Combination With RP1 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 231
- 试验地点
- 56
- 主要终点
- Objective Response Rate (ORR) according to blinded independent review
研究概览
简要总结
To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.
详细描述
RP1 is a selectively replication competent herpes simplex virus type 1(HSV-1). This is a Phase 1/2, open-label, multicenter repeat-dosing study of RP1 alone and in combination with nivolumab in patients with advanced malignancies, and contains both single agent dose escalation, dose expansion to include nivolumab, and the combination in multiple Phase 2 cohorts in individual tumor types.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 confirmed locally advanced or metastatic cutaneous squamous cell carcinoma
- •Patients with locally advanced disease who are not suitable candidates for surgical or radiological treatment of lesions or have refused those treatments
- •At least 1 lesion that is measurable and injectable by study criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patients with ECOG PS 2 at baseline may be allowed to enroll if PS 2 status is only related to the CSCC disease under study
- •Anticipated life expectancy >12 weeks
- •All patients must consent to provide archived or newly obtained tumor material for central pathology review for confirmation of diagnosis of CSCC.
排除标准
- •Prior treatment with an oncolytic therapy
- •Patients with active significant herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis)
- •Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g. acyclovir)
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
- •Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
- •Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant therapy within 3 years.
- •Untreated brain metastasis(es) that may be considered active.
- •Acute or chronic active hepatitis B or known history of hepatitis B or hepatitis C or human immunodeficiency virus (HIV) infection
- •History of ILD/pneumonitis within the last 5 years or a history of ILD/pneumonitis requiring treatment with systemic steroids.
- •Any major or surgical procedure ≤ 28 days before randomization
- •Administration of live vaccines ≤ 28 days before randomization
- •Note: Other protocol defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Cemiplimab in combination with RP1
Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks
干预措施: Cemiplimab (Drug)
Cemiplimab in combination with RP1
Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks
干预措施: RP1 (Biological)
Cemiplimab
Cemiplimab administered intravenously as a single therapy every 3 weeks
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) according to blinded independent review
时间窗: up to 5 years
Complete Response Rate (CRR) according to blinded independent review
时间窗: up to 5 years
次要结局
- Change in overall scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(approximately 30 months)
- Evaluation of the safety and tolerability of cemiplimab alone and combined with RP1 as assessed via adverse events (AEs)(approximately 26 months)
- ORR/CRR for patients who have and have not previously received systemic CSCC-directed therapy and blinded independent review(up to 5 years)
- Overall Survival (OS)(up to 5 years)
- Progression Free Survival (PFS) by blinded independent review.(up to 5 years)
- ORR/CRR by investigator assessment and blinded independent review(up to 5 years)
- 3-year survival(3 years)
- ORR/CRR for patients with metastatic or locally advanced disease according to investigator review and blinded independent review(up to 5 years)
- Progression-free Survival (PFS) per investigator review(up to 5 years)
- Duration of Response (DOR) per investigator review and blinded independent review(up to 5 years)