A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02D
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 36
- 主要终点
- Percentage of participants who experience an adverse event (AE)
研究概览
简要总结
Substudy 02D is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of amendment 2 (effective 01DEC2022) enrollment into the treatment arm of pembrolizumab and lenvatinib has been discontinued.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
- •Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
- •If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
- •Lenvatinib: 7 days
- •Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent. OR
- •Uses contraception unless confirmed to be azoospermic
- •Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, or 30 days after the last dose of lenvatinib, whichever occurs last
- •Has adequate organ function
- •Female participants agree to abstain from breastfeeding during the study intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required for each study intervention is:
- •MK-1308A: 120 days
- •MK-3475: 120 days
- •Lenvatinib: 30 days
排除标准
- •Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
- •Has current or history of known leptomeningeal involvement
- •Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
- •Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
- •Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
- •Has an active infection requiring systemic therapy
- •Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
- •Has ocular melanoma
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has known history of immunodeficiency virus (HIV)
- •Has known history of hepatitis B or known hepatitis C virus
- •Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
- •Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
- •Has a history of whole brain irradiation
- •Has received prior radiotherapy within 2 weeks of first dose of study intervention
- •Has had major surgery <3 weeks prior to first dose of study intervention
- •Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
- •Has had an allogeneic tissue/solid organ transplant
研究组 & 干预措施
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab/Quavonlimab (Biological)
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Lenvatinib (Drug)
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Percentage of participants who experience an adverse event (AE)
时间窗: Up to ~28 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
Percentage of participants who discontinue study treatment due to an AE
时间窗: Up to ~24 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
时间窗: Up to ~30 months
ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
次要结局
- Duration of Response (DOR) per RECIST 1.1(Up to ~30 months)
- Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)(Up to ~30 months)
- Brain metastasis duration of response (BM-DOR) per RANO-BM(Up to ~30 months)
- Progression-free survival (PFS) per RECIST 1.1(Up to ~30 months)