NCT07485049

Phase 0/2 PD-Trigger Study of BGB-58067 in Newly Diagnosed Glioblastoma Patients With MTAP-Deleted Tumors

A Phase 0/2 Study of BGB-58067, an MTA Cooperative PRMT5 Inhibitor, in Newly Diagnosed Glioblastoma Patients With Methylthioadenosine Phosphorylase (MTAP) Deleted Tumors Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With Pharmacodynamic (PD)-Triggered Expansion Cohorts

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: Nader Sanai · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, multi-center, Phase 0/2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067. The study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12). The Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.

Detailed description

PHASE 0 Participants with nGBM will receive a high dose of BGB-58067 prior to surgical resection. The first 5 participants will receive a smaller dose of BGB-58067 to characterize tumor penetration and PD effects at that dose. Participants without histologically confirmed diagnosis of GBM after the craniotomy will be replaced. MTAP-deletion will be determined using IHC on gadolinium (Gd) enhancing tumor tissue collected during resection, which may be supported by retrospective analysis of next-generation sequencing results. Participants with tumors demonstrating PD response will be eligible to enroll into the Phase 2 component. A positive PD response will be defined as a ≥ 50% decrease in SDMA expression relative to baseline biopsy tissue, if available. In the absence of a pretreatment biopsy, an H-score of 70 or below will be deemed as a positive PD response. Eligible participants will then be allocated into one of two Arms based on MGMT methylation status. Participants with unmethylated tumors will be enrolled into Arm A and participants with methylated tumors will be enrolled into Arm B. Participants that do not proceed to the Phase 2 component will receive treatment per treating physician's recommendation. All participants will complete the end of treatment visit, safety follow-up, and survival monitoring. PHASE 2 ARM A Participants with unmethylated-MGMT and MTAP-deleted GBM demonstrating a positive PD response will continue BGB-58067 treatment concurrently with standard of care upfront radiotherapy (RT). Following completion of RT, participants will receive adjuvant monotherapy with BGB-58067 administered continuously. Study visits, safety assessments, and cycle numbering during adjuvant therapy will follow a fixed days cycle calendar. Participants will receive BGB-58067 until disease progression, unacceptable toxicity or death, withdrawal of consent, loss to follow up, or study termination by the sponsor. ARM B Participants with methylated-MGMT and MTAP-deleted GBM demonstrating a positive PD response will continue BGB-58067 treatment concurrently with standard of care upfront RT and temozolomide (TMZ). Following completion of RT, participants will continue BGB-58067 dosing. If a transition period occurs between completion of concurrent therapy and initiation of adjuvant TMZ, BGB-58067 dosing may be continued to maintain uninterrupted exposure. Adjuvant therapy will then begin with BGB-58067 administered on a continuous dosing schedule combined with TMZ. Study visits, safety assessments, and cycle numbering during adjuvant therapy will follow a fixed days cycle calendar. BGB-58067 will have no planned off-days during TMZ cycles. Following completion of TMZ therapy, BGB-58067 may be administered at the same dose received during adjuvant TMZ therapy until disease progression, unacceptable toxicity, withdrawal of consent, loss to follow up, or study termination by the sponsor. ALL PARTICIPANTS. All participants will return to the clinic for safety monitoring following BGB-58067 treatment discontinuation and will be contacted approximately every 3 months for up to 24 months for survival data collection. The start of follow-up for long-term survival will begin after the safety follow-up visit. MRI scans and review in guidance with RANO criteria will occur approximately every 2-3 months, per standard of care, to monitor disease progression. Longitudinal biomarker analysis through liquid biopsy may be conducted to characterize genomic and/or transcriptomic changes from circulating tumor cells (CTCs) or cell free DNA (cfDNA) isolated from CSF collected during Phase 0 surgery, during Phase 2, or at recurrent craniotomy. At the treating investigator's discretion, an Ommaya reservoir or shunt may be placed during Phase 0 surgery to access CSF from the resection cavity. CSF samples will be collected during Phase 2 only if a participant has the Ommaya reservoir in place. Additional biomarker analysis may be conducted using surgical tissue. If the participant undergoes repeat craniotomy for recurrence or disease progression, to enable longitudinal sample collection and analysis, IVY will request samples from the resected tumor, CSF, or blood to help identify possible resistance mechanisms.

Conditions

• Glioblastoma (GBM)

Interventions

Type	Name	Description
DRUG	BGB-58067	During Phase 0, a high dose of BGB-58067 will be administered over several days prior to surgery to determine PK and PD effect in resected tumor tissue. During Phase 2, BGB-58067 dosing will continue with standard radiation therapy (RT) followed with adjuvant therapy. Participants will receive monotherapy or concurrent therapy with temozolomide (TMZ) based on MGMT methylation status.

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-04-01
• Completion: 2028-04-01
• First posted: 2026-03-20
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study