Belvarafenib for CNS Efficacy in Patients With BRAF-Altered Solid Tumors

NCT07688356 | Recruiting Phase 2

• 1 other identifier: 2026-03-119
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, open-label, single-arm clinical study designed to evaluate the efficacy and safety of Belvarafenib in patients with BRAF-altered primary brain tumors (Cohort 1) and metastatic brain tumors (Cohort 2). Eligible patients are those with a confirmed BRAF alteration identified by next-generation sequencing (NGS). Patients who meet the eligibility criteria will receive a detailed explanation of the study, including its purpose, procedures, potential benefits, and risks. Only patients who voluntarily provide written informed consent will be enrolled. All enrolled patients will receive Belvarafenib monotherapy at a dose of 450 mg twice daily (BID). The study drug will be taken orally within 30 minutes after meals with at least 200 mL of water, preferably at approximately 12-hour intervals each day. One treatment cycle is defined as 28 consecutive days of continuous dosing without a planned treatment break. Patients will receive treatment for six cycles (approximately six months) as the initial treatment period. Treatment may be extended or discontinued earlier at the investigator's discretion based on clinical benefit, disease status, and tolerability. During the study, patients will undergo regular clinical evaluations, including physical examinations, vital sign assessments, laboratory tests, and monitoring for adverse events. Radiologic assessments using MRI and/or CT will be performed at scheduled intervals to evaluate tumor response and disease progression. The study aims to determine whether Belvarafenib can control tumor growth, delay disease progression, and improve clinical outcomes in patients with BRAF-altered brain tumors. If treatment-related toxicities occur, dose reductions are permitted according to the protocol. The dose may be reduced from 450 mg BID to 300 mg BID, and subsequently to 200 mg BID, if clinically indicated. Temporary treatment interruption may also be implemented until toxicity resolves. If unacceptable toxicity persists despite dose modification, treatment will be permanently discontinued. Study treatment may be discontinued if any of the following occurs: confirmed disease progression, unacceptable toxicity, withdrawal of informed consent, inability to comply with the study protocol, receipt of other anticancer therapies that may interfere with study outcomes, or if the investigator determines that continued treatment is no longer in the patient's best interest. However, if radiologic disease progression is observed but the investigator determines that the patient continues to derive clinical benefit, treatment beyond progression may be considered after discussion with the sponsor, with appropriate documentation of the rationale. After discontinuation of study treatment, patients will receive the most appropriate subsequent management, including best supportive care (BSC) or other anticancer therapies, as determined by the treating investigator. Follow-up assessments will continue according to the study protocol. The primary objective of this study is to evaluate the efficacy of Belvarafenib in patients with BRAF-altered primary and metastatic brain tumors, while also assessing its safety profile. The results of this study are expected to provide important clinical evidence supporting the development of new treatment strategies for patients with BRAF-altered brain tumors.

Conditions

Primary Brain Tumor; Metastatic Brain Tumor

Keywords

Belvarafenib; Pan-RAF inhibitor; BRAF alteration; Primary brain tumor; Brain metastases; Central nervous system; Targeted therapy; Precision oncology

Outcome Measures

Primary Outcomes (2)

• Primary Cohort 1. 6-Month Progression-Free Survival (6m-PFS)

  Percentage of participants who remain alive without disease progression at 6 months, assessed according to RANO version 2.0.

  6 months

• Primary Cohort 2. 6-Month Progression-Free Survival

  Percentage of participants who remain alive without disease progression at 6 months, assessed according to RANO-BM.

  6 months

Secondary Outcomes (9)

• Progression-Free Survival (PFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Cohort 1: Primary Brain Tumors Confirmed Objective Response Rate (cORR)

  Up to 24 months

• Cohort 2: Metastatic Brain Tumors Confirmed Objective Response Rate (cORR)

  Up to 24 months

• Cohort 1: Primary Brain Tumors Duration of Response (DoR)

  Up to 24 months

Other Outcomes (1)

• Change from Baseline in PROMIS Global Health Score

  Baseline through end of treatment (up to 24 months)

Study Arms (2)

Cohort 1: Primary Brain Tumors

EXPERIMENTAL

Patients with recurrent or refractory BRAF-mutant (including V600E and BRAF fusion mutations) primary brain tumors will receive Belvarafenib.

Drug: Belvarafenib

Cohort 2: Metastatic Brain Tumors

EXPERIMENTAL

Patients with recurrent or refractory BRAF-mutant (including V600E and BRAF fusion mutations) metastatic brain tumors will receive Belvarafenib.

Drug: Belvarafenib

Interventions

Belvarafenib DRUG

Belvarafenib is an oral pan-RAF inhibitor administered at a dose of 450 mg twice daily (BID) in continuous 28-day treatment cycles. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, death, or investigator decision. The study evaluates the efficacy and safety of Belvarafenib in patients with recurrent or refractory BRAF-mutant (including V600E and BRAF fusion mutations) primary brain tumors and metastatic brain tumors.

Cohort 1: Primary Brain Tumors; Cohort 2: Metastatic Brain Tumors

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 19 years or older.
• Histologically confirmed primary brain tumor or metastatic brain tumor.
• Documented BRAF mutation, including point mutations (e.g., V600E) or BRAF fusion mutations.
• Willing and able to provide written informed consent prior to participation in the study.
• Estimated life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ function demonstrated by laboratory assessments performed within 14 days prior to the first dose of study treatment, meeting all of the following criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100 × 10⁹/L
• PT/INR and aPTT ≤ 1.5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert syndrome)
• AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN in patients with liver metastases)
• Alkaline phosphatase ≤ 2.5 × ULN (≤ 5 × ULN in patients with liver or bone metastases)
• Albumin ≥ 2.5 g/dL

You may not qualify if:

• History of hypersensitivity to BRAF inhibitors or related compounds. Prior treatment with a BRAF inhibitor is permitted.
• Presence of hematologic malignancy or double primary malignancies at screening. The following second primary malignancies are permitted:
• Carcinoma in situ of the cervix successfully treated at least 1 year before enrollment;
• Papillary thyroid carcinoma treated with curative surgical resection;
• Completely resected cutaneous squamous cell carcinoma.
• Any of the following:
• \- Receipt of an investigational medicinal product within 28 days or within five half-lives (whichever is longer) before the first dose of study treatment;
• \- Major surgery within 28 days before the first dose of study treatment;
• Newly initiated or recently increased systemic corticosteroid therapy equivalent to ≥10 mg/day of prednisolone within 28 days before the first dose.
• Patients receiving a stable dose for at least 2 weeks or requiring continued corticosteroid treatment after surgery may be enrolled at the investigator's discretion;
• Current treatment with systemic immunosuppressive agents or anticipated need for continuous systemic immunosuppression during the study. Topical preparations, inhaled corticosteroids, ophthalmic preparations, and local injections are permitted;
• More than five prior systemic anticancer treatment regimens.
• Unresolved adverse events of CTCAE Grade ≥2 from previous anticancer therapy at screening, except alopecia.
• Any of the following cardiovascular conditions:
• Mean QTcF \>440 msec;

Sponsors & Collaborators

• Hanmi Pharm: collaborator
• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Hyun Ae Jung, MD, PhD

CONTACT

+82-2-; hyunae0608.jung@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients with recurrent or refractory BRAF-mutant (including V600E mutations and BRAF fusion mutations) primary brain tumors and metastatic brain tumors will be enrolled into two independent cohorts. Approximately 15 patients per cohort will receive Belvarafenib treatment. No concurrent control group will be included; study outcomes will be compared with published literature and/or real-world data as appropriate.

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 7, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)