A Phase 3, Multicenter, Randomized, Open-label, Parallel Group, Treatment Study to Assess the Efficacy and Safety of the Lifileucel (LN-144, Autologous Tumor Infiltrating Lymphocytes [TIL]) Regimen in Combination With Pembrolizumab Compared With Pembrolizumab Monotherapy in Participants With Untreated, Unresectable or Metastatic Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 670
- 试验地点
- 151
- 主要终点
- Objective Response Rate and Progression Free Survival
研究概览
简要总结
This is a Phase 3, multicenter, open-label, randomized, parallel group, treatment study to assess the efficacy and safety of lifileucel in combination with pembrolizumab compared with pembrolizumab alone in participants with untreated, unresectable or metastatic melanoma. Participants randomized to the pembrolizumab monotherapy arm who subsequently have a blinded independent central review- verified confirmed progressive disease (PD) will be offered lifileucel monotherapy in an optional crossover period.
详细描述
The study will enroll participants with unresectable or metastatic melanoma (Stage IIIC, IIID, or IV per the American Joint Committee on Cancer [AJCC] staging system) who have had no prior therapy for metastatic disease. Previous adjuvant/neoadjuvant therapy with a single line of protooncogene B-Raf (BRAF) inhibitor with or without a mitogen-activated protein kinase (MEK) inhibitor, PD-1 inhibitor, or cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4] inhibitor is allowed, provided such treatment was completed ≥6 months before progression to metastatic disease.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has a histologically or pathologically confirmed diagnosis of Stage IIIC, IIID, or IV unresectable or metastatic melanoma.
- •In the investigator's assessment, the participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and an estimated life expectancy of > 6 months.
- •Participant is assessed as having at least one resectable lesion (or aggregate lesions) for lifileucel generation.
- •Participant must have at least one measurable disease as defined by RECIST 1.1 following tumor resection.
- •Participants must have adequate organ function.
- •Participants of childbearing potential or those with partners of childbearing potential must be willing to practice an approved method of highly effective birth control.
- •Participants who are > 70 years of age may be allowed to enroll after the investigator discusses with the medical monitor.
排除标准
- •Participant has melanoma of uveal/ocular origin.
- •Participant has symptomatic untreated brain metastases.
- •Participant received more than 1 prior line of therapy.
- •Participant received prior therapy for metastatic disease
- •Participants with a BRAF V600 mutation-positive tumor received prior adjuvant/neoadjuvant ICI therapy only
- •Participant has an active medical illness(es) that, in the opinion of the investigator, would pose increased risks for study participation, such as systemic infections; seizure disorders; coagulation disorders; or other active major medical illnesses of the cardiovascular, respiratory, or immune systems.
- •Participant has any form of primary or acquired immunodeficiency (eg, SCID or AIDS).
- •Participant had another primary malignancy within the previous 3 years (except for those that do not require treatment or were curatively treated >1 year ago, and in the judgment of the investigator do not pose a significant risk of recurrence.)
- •Participant has a history of allogeneic cell or organ transplant.
- •Other protocol defined inclusion/exclusion criteria could apply.
研究组 & 干预措施
Arm A
Lifileucel plus Pembrolizumab
干预措施: Lifileucel plus Pembrolizumab (Biological)
Arm B
Pembrolizumab alone with Optional Crossover Period
干预措施: Pembrolizumab with Optional Crossover Period (Biological)
结局指标
主要结局
Objective Response Rate and Progression Free Survival
时间窗: 5 years total duration
To compare the efficacy of lifileucel plus pembrolizumab with the efficacy of pembrolizumab alone measured by objective response rate (ORR) and progression-free survival (PFS) assessed by the blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
次要结局
- Complete Response Rate, Duration of Response and Event Free Survival(5 years total duration)
- Objective Response Rate, Progression Free Survival, Complete Response Rate, Duration of Responses, Event Free Survival and PFS2(5 years total duration)
- Overall Survival(7 years total duration)
- Adverse Events(5 years total duration)