An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors [IGNYTE]
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 340
- 试验地点
- 79
- 主要终点
- Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1
研究概览
简要总结
The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).
详细描述
RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory solid tumors. The study will include a dose escalation phase for single agent RP1, an expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified tumor types for the combination therapy.
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
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •At least one measurable and injectable lesion
- •Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
- •Have a predicted life expectancy of ≥ 3 months
- •Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
- •Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy.
- •Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment.
- •Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
- •Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-
- •The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment.
排除标准
- •Prior treatment with an oncolytic therapy
- •History of viral infections according to the protocol
- •Prior complications with herpes infections
- •Chronic use of anti-virals
- •Uncontrolled/untreated brain metastasis
- •History of interstitial lung disease
- •History of non-infectious pneumonitis
- •History of clinically significant cardiovascular disease
研究组 & 干预措施
RP1 (IT) and nivolumab (IV) in melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
干预措施: nivolumab (Biological)
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
干预措施: RP1 (Biological)
RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
干预措施: nivolumab (Biological)
RP1 (IT) and nivolumab (IV) in melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
干预措施: RP1 (Biological)
Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
anti-PD-1 monoclonal antibody
干预措施: RP1 (Biological)
Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
干预措施: RP1 (Biological)
Dose expansion of RP1 and nivolumab (IV) in superficial tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
干预措施: RP1 (Biological)
Dose expansion of RP1 and nivolumab (IV) in superficial tumors
Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
干预措施: nivolumab (Biological)
Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
干预措施: RP1 (Biological)
Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
干预措施: nivolumab (Biological)
RP1 (IT) and nivolumab (IV) in NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
干预措施: RP1 (Biological)
RP1 (IT) and nivolumab (IV) in NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
干预措施: nivolumab (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy
干预措施: RP1 (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy
干预措施: nivolumab (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
干预措施: RP1 (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
干预措施: nivolumab (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
干预措施: RP1 (Biological)
RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
干预措施: nivolumab (Biological)
结局指标
主要结局
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1
时间窗: 20 weeks
Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation
Percentage of adverse events (AEs)
时间窗: 26 months
Percentage of subjects with adverse events (AEs)
Percentage of serious adverse events (SAEs)
时间窗: 26 months
Percentage of subjects with serious adverse events (SAEs)
Percentage of overall response rate (ORR)
时间窗: 26 months
Percentage of overall response rate (ORR) for all participants
Percentage of dose limiting toxicities (DLTs)
时间窗: 26 months
Percentage of subjects with dose limiting toxicities (DLTs)
次要结局
- Percentage of complete response (CR)(26 months)
- Median overall survival(26 months)
- Percentage subjects with detectable RP1(20 weeks)
- Median duration of response(26 months)
- Median progression-free survival(26 months)
- Percentage of biologic activity(20 weeks)
研究者
研究点 (79)
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