A Phase 1/2, Open-label Study of PD-1 Knockout Tumor-infiltrating Lymphocytes (IOV-4001) in Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 21
- 主要终点
- Phase 2: Objective Response Rate (ORR)
研究概览
简要总结
This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC).
详细描述
This study is the first-in-human study of IOV-4001, a genetically modified autologous tumor- infiltrating lymphocytes (TIL) product. IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited TIL, but with the potential for enhanced antitumor activity due to disruption of PDCD1, the gene for programmed cell death protein-1 (PD-1).
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have a confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma or Stage III or IV NSCLC.
- •Participants who have received the following previous therapy:
- •Cohort 1 (Melanoma): Participants who have progressed within 12 weeks of last dose of anti-PD-1/PD-L1 blocking antibody and received BRAF/MEK inhibitor in those with BRAF mutations.
- •Cohort 2 (NSCLC): Participants who should have received no more than 3 prior lines of therapy and:
- •those without oncogene-driven tumors: Have progressed within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody
- •those with oncogene-driven tumors: Have progressed during/after ≥1 targeted therapy AND either:
- •platinum doublet chemotherapy
- •Or within 12 weeks after last dose of anti-PD-1/PD-L1 blocking antibody
- •Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Participants who is assessed as having at least one resectable lesion.
- •Participants who have at least one measurable lesion, following resection of the lesion for IOV-4001 generation.
- •Participants who have adequate organ function.
- •Cardiac function test required.
- •Pulmonary function test may be required.
- •Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control during treatment and up to 12 months.
- •Participants who are >70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.
排除标准
- •Participants who have melanoma of uveal/ocular origin.
- •Participants who have symptomatic untreated brain metastases.
- •Participants who have had a history of allogeneic organ transplant or any form of cell therapy involving prior conditioning chemotherapy within the past 20 years.
- •Participants who require systemic steroid therapy 10 mg/day prednisone or another steroid equivalent dose.
- •Participants who have any form of primary immunodeficiency.
- •Participants who have another primary malignancy within the previous 3 years.
- •Participants who have received or will receive a live or attenuated vaccination within 28 days prior to the start of the NMA-LD.
研究组 & 干预措施
Cohort 1
Participants with unresectable or metastatic melanoma
干预措施: IOV-4001 (Biological)
Cohort 2
Participants with Stage III or IV non-small-cell lung cancer
干预措施: IOV-4001 (Biological)
结局指标
主要结局
Phase 2: Objective Response Rate (ORR)
时间窗: Up to 60 months
To evaluate the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the investigator
Phase I: Safety of IOV-4001
时间窗: Up to 1 Year or depending on when the recommended phase 2 dose is determined
The safety of IOV-4001 will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase
次要结局
- CR Rate(Up to 60 months)
- Duration of Response (DOR)(Up to 60 months)
- Disease Control Rate (DCR)(Up to 60 months)
- Progression-free Survival (PFS)(Up to 60 months)
- Overall Survival (OS)(Up to 60 months)
- Safety and Tolerability of IOV-4001(Up to 60 months)
- Feasibility of IOV-4001(Up to 60 months)