A Study of Pembrolizumab in Combination With Investigational Agents in Pediatric and Young Adult Participants With Hematologic Malignancies or Solid Tumors (MK-9999-01B/LIGHTBEAM-U01)

Neoplasm Metastasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06395090
• Other study ID #: 9999-01B
• Secondary ID: MK-9999-01BLIGHT
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: July 5, 2024
• Est. completion date: June 30, 2029

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The master screening protocol is MK-9999-U01.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: June 30, 2029
• Est. primary completion date: June 30, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Neoplasm Metastasis

Intervention

Biological:
• Pembrolizumab
IV infusion
• Favezelimab
IV infusion
• Favezelimab/Pembrolizumab
IV infusion
• Vibostolimab
IV infusion
• Pembrolizumab/Vibostolimab
IV infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 1: 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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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 60 months
Primary	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 60 months
Secondary	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.	Up to approximately 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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 60 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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 60 months

External Links

•   Merck Clinical Trials Information