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 02B
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 335
- 试验地点
- 120
- 主要终点
- Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase
研究概览
简要总结
Substudy 02B is part of a larger research study where researchers are looking for new ways to treat advanced melanoma that has not been treated before. The larger study is the umbrella study. Researchers want to know if adding other treatments to pembrolizumab can treat advanced melanoma. The goals of this study are to learn:
- About the safety and how well people tolerate pembrolizumab given with other treatments
- How many people have melanoma that responds (gets smaller or goes away) to treatment
详细描述
With Amendment 6, all arms are closed to enrollment. Participants in arms 2 (pembrolizumab), 3 (coformulation pembrolizumab/quavonlimab), and 4 (coformulation pembrolizumab/quavonlimab + lenvatinib) who complete study treatment or otherwise meet end of treatment (EOT) criteria will be discontinued from the study after completing the EOT visit and any required safety follow-up visits. Participants in arm 6 (coformulation favezelimab/pembrolizumab + All-trans Retinoic Acid [ATRA]) will discontinue ATRA and participants in arms 5 and 6 can continue on coformulation favezelimab/pembrolizumab or pembrolizumab.
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 histologically or cytologically confirmed melanoma
- •Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
- •Has been untreated for advanced disease.
- •Has provided a tumor biopsy
- •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 (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
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- •Is not a WOCBP OR
- •Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) 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:
- •MK-4280A: 120 days
- •MK-1308A: 120 days
- •MK-7684: 50 days
- •MK-3475: 120 days
- •Lenvatinib: 30 days
- •ATRA: 30 days
- •Has adequate organ function
- •Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)
排除标准
- •Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
- •Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
- •Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has ocular or mucosal melanoma
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years
- •Has an active infection requiring systemic therapy
- •Has known history of human immunodeficiency virus (HIV)
- •Has history of Hepatitis B or known Hepatitis C virus infection
- •Has a history of (noninfectious) pneumonitis
- •Has a history of active tuberculosis (TB)
- •Has received prior systemic anticancer therapy within 4 weeks prior to randomization
- •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 vaccine within 30 days before the first dose of study intervention
- •Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
- •Has had an allogeneic tissue/solid organ transplant
- •Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
- •Participants who receive lenvatinib have the following additional exclusion criteria:
- •Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- •Has radiographic evidence of encasement of invasion of a major blood vessel, or of intratumoral cavitation
- •Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
- •Has urine protein ≥1 g/24-hour.
- •Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
研究组 & 干预措施
Pembrolizumab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Vibostolimab (Biological)
Pembrolizumab + Vibostolimab
Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV 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
Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Coformulation Favezelimab/Pembrolizumab
Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years
干预措施: Favezelimab/Pembrolizumab (Biological)
Coformulation Favezelimab/Pembrolizumab + Vibostolimab
Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Vibostolimab (Biological)
Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA)
Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).
干预措施: ATRA (Drug)
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive coformulation of pembrolizumab and quavonlimab 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 Favezelimab/Pembrolizumab + Vibostolimab
Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Favezelimab/Pembrolizumab (Biological)
Coformulation Pembrolizumab/Quavonlimab
Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
干预措施: Pembrolizumab/Quavonlimab (Biological)
Pembrolizumab
Participants will receive pembrolizumab IV at a specified dose 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 coformulation of pembrolizumab and quavonlimab 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 coformulation of pembrolizumab and quavonlimab 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 a dose-limiting toxicity (DLT): Safety lead-in phase
时间窗: Up to ~3 weeks
The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported.
Percentage of participants who experience an adverse event (AE): Safety lead-in
时间窗: Up to ~3 weeks
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 during the safety lead-in period will be reported.
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 least a 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.
Percentage of participants who discontinue study treatment due to an AE: Safety lead-in
时间窗: Up to ~3 weeks
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 during the safety lead-in will be reported.
次要结局
- Duration of Response (DOR) per RECIST 1.1(Up to ~30 months)