A Study of Belzutifan in Adolescent Participants With Solid Tumors (MK-9999-01E/LIGHTBEAM-U01)

LIGHTBEAM-U01 Substudy 01E: A Phase 2 Substudy to Evaluate the Safety and Efficacy of Belzutifan in Participants With Solid Tumors

Researchers are looking for new ways to treat adolescents with locally advanced, unresectable, or metastatic solid tumors. Participants were enrolled into pheochromocytoma/paraganglioma (PPGL), wild type gastrointestinal stromal tumor (wtGIST), and Von Hippel-Lindau (VHL) disease-associated localized tumors cohorts:

• PPGL are rare cancers that start in cells that make hormones in the adrenal glands
• wtGIST is a less common type of cancer that starts in the digestive tract. Wild type means it does not have certain gene mutations (changes)
• VHL disease-associated localized tumors are rare tumors caused by a certain gene mutation that may be passed down from parents to children
• Locally advanced means the cancer has spread into nearby tissue
• Unresectable means the cancer cannot be removed by surgery
• Metastatic means the cancer has spread to other parts of the body

The goal of the study is to learn about the safety of belzutifan and if people tolerate it.

Study Overview

• Status: Not yet recruiting
• Conditions: Malignant Neoplasm
• Intervention / Treatment: Drug: Belzutifan

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

• Has a diagnosis of one of the following: locally advanced, unresectable, or metastatic pheochromocytoma/paraganglioma or wild-type gastrointestinal stromal tumors, or localized tumors associated with von Hippel-Lindau disease
• Has measurable disease per RECIST 1.1

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has clinically significant cardiac disease or electrocardiogram indicating uncontrolled cardiac condition or has congenital long QT syndrome
• Has a history of human immunodeficiency virus infection
• Has received prior treatment with any hypoxia inducible factor-2α inhibitor, including belzutifan
• Has had an allogenic tissue/solid organ transplant
• Has a history of autologous stem cell transplant within 6 months of start of study intervention
• Has known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has known active central nervous system metastases and/or carcinomatous meningitis
• Has an active infection requiring systemic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belzutifan; Participants will receive belzutifan 80 mg (body weight <40 kg) or 120 mg (body weight ≥40 kg) orally once daily for approximately 2 years.	Drug: Belzutifan; Administered once daily via oral tablet; Other Names: MK-6482, PT2977, WELIREG®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience One or More Adverse Events (AEs)	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. The number of participants that experience AEs will be reported.	Up to approximately 5 years
Number of Participants Who Discontinue Study Intervention 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. The number of participants that discontinue study intervention due to an AE will be reported.	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time 0 to 24 hours of Belzutifan	Blood samples will be collected at specified intervals to determine the area under the concentration-time curve from time 0 to 24 hours of belzutifan.	At designated timepoints (up to 5 weeks)
Minimum Plasma Concentration (Cmin) of Belzutifan	Blood samples will be collected at specified intervals to determine the Cmin of belzutifan.	At designated timepoints (up to 5 weeks)
Maximum Plasma Concentration (Cmax) of Belzutifan	Blood samples will be collected at specified intervals to determine the Cmax of belzutifan.	At designated timepoints (up to 5 weeks)
Objective Response Rate (ORR)	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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by investigator will be reported.	Up to approximately 5 years
Duration of Response (DOR)	For participants who demonstrate a confirmed 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (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 investigator will be reported.	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Estimated): November 23, 2026
• Primary Completion (Estimated): January 2, 2034
• Study Completion (Estimated): January 2, 2034

Study Registration Dates

• First Submitted: July 8, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 14, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; belzutifan
• Other Study ID Numbers: 9999-01E; LIGHTBEAM-U01 (Other Identifier: MSD); U1111-1330-9370 (Registry Identifier: UTN); 2025-524515-37-00 (Registry Identifier: EU CT); MK-9999-01E (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No