Phase 1/2 Study Evaluating the Safety, PK/PD, and Clinical Activity of Oral JBI-778 in Patients With Brain Metastases, Leptomeningeal Disease, or Recurrent High Grade Glioma

NCT07751744 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: JBI-778-101
• Study Type: interventional
• Target: 113
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1/2, multicenter, open-label, dose-escalation and dose-expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), cerebrospinal fluid penetration, and preliminary antitumor activity of orally administered JBI-778, a selective PRMT5 inhibitor, in patients with brain metastases, leptomeningeal disease, or recurrent high-grade glioma. The study consists of a dose-escalation phase to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), followed by expansion cohorts to evaluate preliminary efficacy at the RP2D.

Conditions

Brain Metastases From Solid Tumors; Leptomeningeal Disease; High Grade Glioma (HGG); Glioblastoma (GBM)

Keywords

JBI-778; PRMT5 Inhibitor; Brain Metastases; Leptomeningeal Disease; High-Grade Glioma; Glioblastoma

Outcome Measures

Primary Outcomes (4)

• Phase 1 - Incidence of Dose Limiting Toxicities (DLTs)

  Number of participants with dose-limiting toxicity (DLT) events during the DLT monitoring period. DLTs are defined per protocol criteria and graded using NCI CTCAE Version 5.0.

  At the end of Cycle 1 (each cycle is 21 days)

• Phase 2 High-Grade Glioma Cohort: Objective Response Rate (ORR)

  Investigator-assessed ORR according to Response Assessment in Neuro-Oncology (RANO) criteria.

  Up to 2 years

• Phase 2 Brain Metastases Cohort: Objective Response Rate (ORR)

  Investigator-assessed ORR according to RANO Brain Metastases (RANO-BM) criteria.

  Up to 2 years.

• Phase 2 Leptomeningeal Disease Cohort: Overall Survival (OS)

  Overall survival in participants with leptomeningeal disease.

  Up to 2 years.

Secondary Outcomes (4)

• Incidence of Adverse Events

  Up to 2 years

• Maximum Plasma Concentration (Cmax) of JBI-778

  From Cycle 1 Day 1 up to Cycle 2 Day 1 (each cycle is 21 days)

• Area Under the Plasma Concentration-Time Curve (AUC0-t) of JBI-778

  From Cycle 1 Day 1 up to Cycle 2 Day 1 (each cycle is 21 days)

• Time to Maximum Plasma Concentration (Tmax) of JBI-778

  From Cycle 1 Day 1 up to Cycle 2 Day 1 (each cycle is 21 days)

Study Arms (4)

Arm 1 - Dose-Escalation Phase

EXPERIMENTAL

Intervention Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles

Drug: JBI-778

Arm 2 - High-Grade Glioma Expansion Cohort

EXPERIMENTAL

Intervention Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles

Drug: JBI-778

Arm 3 - Brain Metastases Expansion Cohort

EXPERIMENTAL

Intervention Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles

Drug: JBI-778

Arm 4 - Leptomeningeal Disease Expansion Cohort

EXPERIMENTAL

Intervention Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles

Drug: JBI-778

Interventions

JBI-778 DRUG

Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles

Arm 1 - Dose-Escalation Phase; Arm 2 - High-Grade Glioma Expansion Cohort; Arm 3 - Brain Metastases Expansion Cohort; Arm 4 - Leptomeningeal Disease Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥18 years.
• Histologically or cytologically confirmed:
• Solid tumors with stable brain metastases (Dose Escalation Part), or Recurrent/progressive high-grade glioma, or Brain metastases from NSCLC, breast cancer, or melanoma, or Leptomeningeal disease (Dose Expansion Part).
• Adequate organ function:
• ANC ≥1,500/mm³ Platelets ≥100,000/mm³ Hemoglobin \>8.0 g/dL Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert syndrome) AST/ALT ≤2.5 × ULN (≤5 × ULN if liver metastases present) Creatinine clearance ≥60 mL/min PT/aPTT ≤1.5 × ULN (or stable anticoagulation therapy) At least one measurable lesion on MRI according to applicable RANO criteria, or positive CSF cytology for leptomeningeal disease.
• Resolution of clinically significant toxicities from prior therapy to Grade ≤1 (except alopecia, Grade 2 peripheral neuropathy, or chronic Grade 2 endocrinopathies due to prior immunotherapy).
• ECOG performance status ≤2. Ability to swallow oral medication. Life expectancy ≥3 months. Willing and able to provide written informed consent. Willingness to use effective contraception during treatment and for 3 months after the last dose.
• Histologically or cytologically confirmed solid tumors with stable treated brain metastases and no available effective treatment options.
• Neurologically stable brain metastases without progression or hemorrhage for ≥4 weeks following treatment.
• Off systemic corticosteroids for symptomatic brain metastases for ≥14 days before enrollment.
• Recurrent or progressive high-grade glioma after standard therapy including radiation and temozolomide.
• Brain metastases from melanoma, NSCLC, or breast cancer meeting protocol-defined prior treatment requirements.
• Leptomeningeal disease with protocol-defined prior therapy requirements.

You may not qualify if:

• Systemic anticancer therapy or investigational therapy within 2 weeks or 5 half-lives before first dose.
• Major surgery within 21 days before first dose or not recovered from surgery. Conditions that may significantly impair drug absorption. Radiotherapy within 2 weeks prior to study treatment (except permitted palliative radiation or stereotactic radiosurgery).
• Severe or unstable medical conditions including:
• NYHA Class III/IV heart failure Uncontrolled hypertension Uncontrolled diabetes Significant psychiatric illness Uncontrolled arrhythmias Myocardial infarction within 6 months Congenital long QT syndrome or QTcF \>470 msec. History of optic neuritis or optic neuropathy. Other active malignancy likely to interfere with study assessments. Live vaccine within 30 days before first dose. Known active HIV infection or active hepatitis B or C infection (HCV RNA-negative patients may be eligible).
• Use of strong or moderate CYP3A inhibitors within 14 days or 5 half-lives before Cycle 1 Day 1, or grapefruit-containing products within 7 days.
• Active gastrointestinal disease or malabsorption syndrome affecting drug absorption.
• Acute illness within 14 days before first dose unless approved by investigator and sponsor.
• Active infection requiring systemic antimicrobial or antiviral therapy not completed before treatment.
• Pregnant or breastfeeding women. Concurrent participation in another investigational drug study. Previous treatment with JBI-778 in this study. Any condition that, in the investigator's opinion, places the patient at unacceptable risk or prevents compliance with study requirements.
• For Dose Escalation Part only: ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of brain metastases (except protocol-permitted low-dose corticosteroids).

Sponsors & Collaborators

• Jubilant Therapeutics Inc.: lead

MeSH Terms

Conditions

Meningeal Neoplasms; Glioma; Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Brain Diseases; Central Nervous System Diseases

Central Study Contacts

Melda Dolan, MD

CONTACT

3144989959; Melda.Dolan@jubl.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants receive oral JBI-778. Dose levels vary during dose-escalation and expansion phases. Drug: JBI-778 Oral capsule Strengths: 20 mg, 100 mg, 250 mg Starting dose: 40 mg daily Continuous once-daily administration in 21-day cycles Administered under fasting conditions

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 7, 2026
• Study Start (Estimated): April 1, 2028
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: August 7, 2026

Record last verified: 2026-08