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)

NCT06395090 | Withdrawn Phase 1 DMC FDA Drug

• 5 other identifiers: 9999-01BMK-9999-01BLIGHTBEAM-U012023-507179-23U1111-1295-3472
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 12

Brief 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). 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.

Conditions

Neoplasm Metastasis

Outcome Measures

Primary Outcomes (8)

• 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.

  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

Secondary Outcomes (13)

• 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

Study Arms (4)

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.

Biological: Pembrolizumab; Biological: Favezelimab

Favezelimab/Pembrolizumab

EXPERIMENTAL

Participants will receive coformulated favezelimab/pembrolizumab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Biological: Favezelimab/Pembrolizumab

Pembrolizumab + Vibostolimab

EXPERIMENTAL

Participants will receive pembrolizumab and vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Biological: Pembrolizumab; Biological: Vibostolimab

Pembrolizumab/Vibostolimab

EXPERIMENTAL

Participants will receive coformulated pembrolizumab/vibostolimab via an IV infusion Q3W for up to 35 cycles. Each cycle is 21 days.

Biological: Pembrolizumab/Vibostolimab

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475

Favezelimab + Pembrolizumab; Pembrolizumab + Vibostolimab

Favezelimab BIOLOGICAL

IV infusion

Favezelimab + Pembrolizumab

Favezelimab/Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-4280A

Favezelimab/Pembrolizumab

Vibostolimab BIOLOGICAL

IV infusion

Pembrolizumab + Vibostolimab

Pembrolizumab/Vibostolimab BIOLOGICAL

IV infusion

Also known as: MK-7684A

Pembrolizumab/Vibostolimab

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must have 1 of the following histologically or cytologically confirmed diagnosis of Relapsed or refractory classical Hodgkin lymphoma (cHL) 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (12)

Yale-New Haven Hospital ( Site 2012)

New Haven, Connecticut, 06510, United States

Location

University of Iowa-Holden Comprehensive Cancer Center ( Site 2017)

Iowa City, Iowa, 52242, United States

Location

Children's Mercy Hospital ( Site 2024)

Kansas City, Missouri, 64108, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 2008)

New Brunswick, New Jersey, 08903, United States

Location

New York Medical College ( Site 2023)

Valhalla, New York, 10595, United States

Location

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 2003)

Fargo, North Dakota, 58122, United States

Location

Children's Hospital of Philadelphia (CHOP) ( Site 2021)

Philadelphia, Pennsylvania, 19104, United States

Location

Sanford Children's Hospital-Sanford Children's Specialty Clinic ( Site 2015)

Sioux Falls, South Dakota, 57105, United States

Location

Intermountain - Primary Children's Hospital ( Site 2014)

Salt Lake City, Utah, 84113, United States

Location

Seoul National University Hospital-Pediatrics ( Site 2972)

Seoul, 03080, South Korea

Location

Asan Medical Center-Pediatrics - Pedicatric Oncology ( Site 2973)

Seoul, 05505, South Korea

Location

National Taiwan University Hospital ( Site 2983)

Taipei, 10002, Taiwan

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 1, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

TW (1); US (9); KR (2)