Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| MK-9999-01B | Other Identifier | MSD | |
| LIGHTBEAM-U01 | Other Identifier | MSD | |
| 2023-507179-23 | Registry Identifier | EU CT | |
| U1111-1295-3472 | Registry Identifier | UTN |
Not provided
Not provided
Not provided
development program discontinuation
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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). 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.
The master screening protocol is MK-9999-U01.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Favezelimab + Pembrolizumab | Experimental | 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. |
|
| Favezelimab/Pembrolizumab | Experimental | Participants will receive coformulated favezelimab/pembrolizumab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days. |
|
| Pembrolizumab + Vibostolimab | Experimental | Participants will receive pembrolizumab and vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days. |
|
| Pembrolizumab/Vibostolimab | Experimental | Participants will receive coformulated pembrolizumab/vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Biological | IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants Who Experience Dose-limiting Toxicities (DLTs) | 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. | Up to 21 days |
| Parts 1 and 2: Number of Participants Who Report at Least 1 Adverse Event (AE) | 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. | Up to approximately 27 months |
| Parts 1 and 2 : Number of Participants Who Discontinue Study Drug Due to an AE | 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. | Up to approximately 24 months |
| Part 1: Area Under the Curve (AUC) | Blood samples will be collected at specified intervals for the determination of 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 1: Maximum Concentration (Cmax) | Blood samples will be collected at specified intervals for the determination of Cmax. |
| Measure | Description | Time Frame |
|---|---|---|
| Parts 1 and 2: ORR per Lugano Response Criteria by Investigator | DCR is defined as the percentage of the participants who have stable disease (SD), CR or PR. Response is assessed by CT and PET-CT and evaluated based on Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal 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 SPD for up to 6 target measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by >50% beyond normal). SD is no significant change from baseline in response and no criteria met for progressive disease. DCR as assessed by the investigator will be presented. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale-New Haven Hospital ( Site 2012) | New Haven | Connecticut | 06510 | United States | ||
| University of Iowa-Holden Comprehensive Cancer Center ( Site 2017) |
Not provided
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
| Plain Language Summary | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Favezelimab | Biological | IV infusion |
|
| Favezelimab/Pembrolizumab | Biological | IV infusion |
|
|
| Vibostolimab | Biological | IV infusion |
|
| Pembrolizumab/Vibostolimab | Biological | IV infusion |
|
|
| 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 1: Concentration in the Blood Immediately Before the Next Dose (Ctrough) | Blood samples will be collected at specified intervals for the determination of 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: Objective Response Rate (ORR) per Lugano Response Criteria by Blinded Independent Central Review (BICR) | 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. | Up to approximately 57 months |
| Parts 1 and 2: ORR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator | 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. | Up to approximately 57 months |
| Up to approximately 57 months |
| Parts 1 and 2: Disease Control Rate (DCR) per Lugano Response Criteria by BICR | DCR is defined, per RECIST 1.1, as the percentage of participants who have a CR: Disappearance of all target lesions or PR: At least a 30% decrease in the sum of diameters of target lesions or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.] The DCR as assessed by BICR will be presented. | Up to approximately 57 months |
| Parts 1 and 2: DCR per RECIST 1.1 by Investigator | DCR is defined, per RECIST 1.1, as the percentage of participants who have a CR: Disappearance of all target lesions or PR: At least a 30% decrease in the sum of diameters of target lesions or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.] The DCR as assessed by BICR will be presented. | Up to approximately 57 months |
| Parts 1 and 2: Duration of Response (DOR) per Lugano Response Criteria by BICR | For participants who demonstrate a confirmed CR or PR, DOR is defined as the time from CR or PR to documented disease progression or death. Participants are assessed using CT and PET-CT and response was evaluated based on the Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). CR is complete metabolic (no/minimal 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 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). DOR as assessed by BICR will be presented. | Up to approximately 57 months |
| Parts 1 and 2: DOR per RECIST 1.1 by Investigator | For participants who demonstrate a confirmed CR: disappearance of all target lesions or PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented. | Up to approximately 57 months |
| Parts 1 and 2: Progression Free Survival (PFS) per Lugano Response Criteria by BICR | PFS is defined as the time from randomization to documented disease progression or death, whichever occurs first as based on Lugano Classification (Cheson et al, Journal of Clinical Oncology, 2014). PFS as assessed by BICR will be presented. | Up to approximately 57 months |
| Parts 1 and 2: PFS per RECIST 1.1 by Investigator | PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by the investigator will be presented. | Up to approximately 57 months |
| Parts 1 and 2: Overall Survival (OS) | OS is defined as time from first dose of study treatment to death due to any cause. | Up to approximately 57 months |
| Part 2: Area Under the Curve (AUC) | Blood samples will be collected at specified intervals for the determination of 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) | Blood samples will be collected at specified intervals for the determination of 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) | Blood samples will be collected at specified intervals for the determination of 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 | Blood samples will be collected at specified intervals for the determination of 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) | For participants with cHL, the biomarker levels for cHL will be reported. | Up to approximately 57 months |
| Iowa City |
| Iowa |
| 52242 |
| United States |
| Children's Mercy Hospital ( Site 2024) | Kansas City | Missouri | 64108 | United States |
| Rutgers Cancer Institute of New Jersey ( Site 2008) | New Brunswick | New Jersey | 08903 | United States |
| New York Medical College ( Site 2023) | Valhalla | New York | 10595 | United States |
| Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2003) | Fargo | North Dakota | 58122 | United States |
| Children's Hospital of Philadelphia (CHOP) ( Site 2021) | Philadelphia | Pennsylvania | 19104 | United States |
| Sanford Children's Hospital-Sanford Children's Specialty Clinic ( Site 2015) | Sioux Falls | South Dakota | 57105 | United States |
| Intermountain - Primary Children's Hospital ( Site 2014) | Salt Lake City | Utah | 84113 | United States |
| Seoul National University Hospital-Pediatrics ( Site 2972) | Seoul | 03080 | South Korea |
| Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 2973) | Seoul | 05505 | South Korea |
| National Taiwan University Hospital ( Site 2983) | Taipei | 10002 | Taiwan |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided