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)

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.

Eligibility Criteria:
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