LIGHTBEAM-U01 Substudy 01B: A Phase 1/2 Substudy to Evaluate the Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 80
- 试验地点
- 12
- 主要终点
- Part 1: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This study is a rolling arm study of pembrolizumab in combination with investigational agents in pediatric participants with relapsed or refractory classical Hodgkin lymphoma (cHL), solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) or tumor mutational burden-high (TMB-H), or advanced melanoma. This study will have 2 parts: a safety lead-in to demonstrate a tolerable safety profile and confirm a preliminary recommended phase 2 dose (RP2D) (Part 1) followed by an efficacy evaluation (Part 2). Participants will be assigned to a treatment arm (either Part 1 or Part 2) that is open for enrollment.
There will be no hypothesis testing in this study.
详细描述
The master screening protocol is MK-9999-U01.
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
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have 1 of the following histologically or cytologically confirmed diagnosis of Relapsed or refractory classical Hodgkin lymphoma (cHL), advanced melanoma, solid tumors that are microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR), or solid tumors that are tumor mutational burden-high (TMB-H)
- •Must have recovered from all AEs from previous anticancer therapies
- •Human immunodeficiency virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy (ART)
排除标准
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- •Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Received prior anticancer therapy with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) in combination with either an Anti- lymphocyte-activation gene 3 (LAG-3) agent or an Anti- T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) agent
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Known additional malignancy that is progressing or has required active treatment within the past 1 year
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active autoimmune disease that has required systemic treatment in the past 2 years
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Active infection requiring systemic therapy
- •Concurrent active Hepatitis B and Hepatitis C virus infection
- •History of allogenic tissue/solid organ transplant
- •Has symptoms of or is being treated for graft versus host disease (GVHD)
- •Has not adequately recovered from major surgery or have ongoing surgical complications
- •Known tumors involving the brainstem
研究组 & 干预措施
Pembrolizumab + Vibostolimab
Participants will receive pembrolizumab and vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.
干预措施: Pembrolizumab (Biological)
Favezelimab + Pembrolizumab
Participants will receive pembrolizumab and favezelimab via an intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 cycles. Each cycle is 21 days.
干预措施: Pembrolizumab (Biological)
Favezelimab + Pembrolizumab
Participants will receive pembrolizumab and favezelimab via an intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 cycles. Each cycle is 21 days.
干预措施: Favezelimab (Biological)
Favezelimab/Pembrolizumab
Participants will receive coformulated favezelimab/pembrolizumab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.
干预措施: Favezelimab/Pembrolizumab (Biological)
Pembrolizumab + Vibostolimab
Participants will receive pembrolizumab and vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.
干预措施: Vibostolimab (Biological)
Pembrolizumab/Vibostolimab
Participants will receive coformulated pembrolizumab/vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.
干预措施: Pembrolizumab/Vibostolimab (Biological)
结局指标
主要结局
Part 1: Number of Participants Who Experience Dose-limiting Toxicities (DLTs)
时间窗: Up to 21 days
The number of participants who experience toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose will be reported.
Parts 1 and 2: Number of Participants Who Report at Least 1 Adverse Event (AE)
时间窗: Up to approximately 27 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Parts 1 and 2 : Number of Participants Who Discontinue Study Drug Due to an AE
时间窗: Up to approximately 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 1: Maximum Concentration (Cmax)
时间窗: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
Blood samples will be collected at specified intervals for the determination of Cmax.
Part 1: Area Under the Curve (AUC)
时间窗: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
Blood samples will be collected at specified intervals for the determination of AUC.
Part 1: Concentration in the Blood Immediately Before the Next Dose (Ctrough)
时间窗: Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days
Blood samples will be collected at specified intervals for the determination of Ctrough.
Parts 1 and 2: Objective Response Rate (ORR) per Lugano Response Criteria by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 57 months
ORR is defined as the percentage of participants who have a complete response (CR) or partial response (PR) and will be evaluated using computed tomography (CT) and positron emission tomography (PET)-CT. Response was assessed based on the International Working Group Criteria: Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PR is partial metabolic (moderate/high FDG uptake) and radiologic response (≥50% decrease in sum of product diameters (SPD) for multiple lesions of up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by \>50% in length beyond normal). The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Parts 1 and 2: ORR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator
时间窗: Up to approximately 57 months
ORR is defined as the percentage of participants with 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) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.
次要结局
- Parts 1 and 2: ORR per Lugano Response Criteria by Investigator(Up to approximately 57 months)
- Parts 1 and 2: Disease Control Rate (DCR) per Lugano Response Criteria by BICR(Up to approximately 57 months)
- Parts 1 and 2: DCR per RECIST 1.1 by Investigator(Up to approximately 57 months)
- Parts 1 and 2: Duration of Response (DOR) per Lugano Response Criteria by BICR(Up to approximately 57 months)
- Parts 1 and 2: DOR per RECIST 1.1 by Investigator(Up to approximately 57 months)
- Parts 1 and 2: Progression Free Survival (PFS) per Lugano Response Criteria by BICR(Up to approximately 57 months)
- Parts 1 and 2: PFS per RECIST 1.1 by Investigator(Up to approximately 57 months)
- Parts 1 and 2: Overall Survival (OS)(Up to approximately 57 months)
- Part 2: Area Under the Curve (AUC)(Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days)
- Part 2: Maximum Concentration (Cmax)(Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days)
- Part 2: Concentration in the Blood Immediately Before the Next Dose (Ctrough)(Cycle 1: Predose, postdose, 3, 8, and 15 days postdose; Cycle 2: predose; Cycle 4: predose and postdose; Cycle 5 predose; once predose every 4 cycles from Cycle 6 up to Cycle 35. A cycle is 21 days)
- Parts 1 and 2: Antidrug Antibody (ADA) Levels(Cycle 1, 2, 4, and 5: predose; once every four cycles from Cycle 6 up to Cycle 35. A cycle is 21 days)
- Parts 1 and 2: Biomarker Levels for Classical Hodgkin Lymphoma (cHL)(Up to approximately 57 months)