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)

Merck Sharp & Dohme (MSD)

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Neoplasm Metastasis

Treatments: Biological: Pembrolizumab/Vibostolimab; Biological: Favezelimab/Pembrolizumab; Biological: Favezelimab; Biological: Pembrolizumab; Biological: Vibostolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06395090

LIGHTBEAM-U01 (Other Identifier)

2023-507179-23 (Registry Identifier)

U1111-1295-3472 (Other Identifier)

9999-01B

MK-9999-01B (Other Identifier)

Details and patient eligibility

About

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.

Full description

The master screening protocol is MK-9999-U01.

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 4 patient groups

Favezelimab + Pembrolizumab

Experimental group

Description:

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.

Treatment:

Biological: Favezelimab

Biological: Pembrolizumab

Favezelimab/Pembrolizumab

Experimental group

Description:

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

Treatment:

Biological: Favezelimab/Pembrolizumab

Pembrolizumab + Vibostolimab

Experimental group

Description:

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

Treatment:

Biological: Vibostolimab

Biological: Pembrolizumab

Pembrolizumab/Vibostolimab

Experimental group

Description:

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

Treatment:

Biological: Pembrolizumab/Vibostolimab