STAR CNS: GB5121 in Adult Patients With Relapsed/Refractory CNS Lymphoma
Study Details
Study Description
Brief Summary
The STAR CNS trial is a 3-part study, comprising a phase 1b dose escalation, dose expansion, and a phase 2, to assess the safety, tolerability, dose-limiting toxicity(ies), maximum tolerated dose, and/or optimal biological dose, determine the recommended phase 2 dose, preliminary anti-tumor activity and efficacy of the recommended phase 2 dose of GB5121.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GB5121 GB5121 orally twice per day (BID) |
Drug: GB5121
Capsule containing GB5121
|
Outcome Measures
Primary Outcome Measures
- Phase 1b Dose Escalation - Incidence of Adverse Events [From first dose until 28 days after the last dose of GB5121]
- Phase 1b Dose Escalation - Dose Limiting Toxicity(ies) [From Cycle 1, Day 1 through Cycle 1, Day 28 inclusive, Each Cycle=28 days]
- Phase 1b Dose Escalation - Serious Adverse Events [From consent until 28 days after the last dose of GB5121]
- Phase 1b Dose Escalation - Optimal Biologic Dose and/or Maximum Tolerated Dose and Recommended Phase 2 Dose [From first dose up to approximately 36 months]
- Phase 1b Dose Expansion - Incidence of Adverse Events [From first dose until 28 days after the last dose of GB5121]
- Phase 1b Dose Expansion - Serious Adverse Events [From consent until 28 days after the last dose of GB5121]
- Phase 2 - Objective Response Rate According to International Primary CNS Lymphoma Collaborative Group (IPCG) Criteria by Blinded Independent Central Review Committee (BICR) [From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
Secondary Outcome Measures
- Phase 1b Dose Expansion - Objective Response Rate According to IPCG Criteria by Investigator Assessment [From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Duration of Response by BICR Committee [From first observation of complete response, unconfirmed complete response or partial response until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Confirmed Complete Response by BICR Committee [From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Objective Response Rate According to the IPCG Criteria by Investigator Assessment [From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Median Progression-Free Survival [From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Progression-Free Survival at Week 24 [From Study Day 1 until Week 24]
- Phase 2 - Overall Survival [From Study Day 1 until death, unacceptable toxicity, or discontinuation, up to approximately 36 months]
- Phase 2 - Incidence of Adverse Events [From first dose until 28 days after the last dose of GB5121]
- Phase 2 - Incidence of Serious Adverse Events [From consent until 28 days after the last dose of GB5121]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically/cytologically confirmed primary central nervous system lymphoma (PCNSL), primary vitreoretinal lymphoma (PVRL), or CNS-only High-Grade B-cell lymphoma or CNS involvement with systemic High-Grade B-cell lymphoma (DLBCL/SCNSL).
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All patients must have relapsed/refractory disease and have received at least one prior CNS-directed therapy.
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Patients must be able to tolerate gadolinium-enhanced magnetic resonance imaging (MRI) scans, or contrast-enhanced computed tomography (CT).
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Patients with parenchymal lesions must have baseline imaging (gadolinium-enhanced MRI or if contraindicated, measurable CT, of the brain) within 28 days prior to first study drug dose. For patients with leptomeningeal disease only, cerebrospinal fluid (CSF) cytology must document lymphoma cells and/or imaging findings consistent with CSF disease after informed consent and prior to first study dose (at the discretion of the Investigator).
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Patients with parenchymal lesions must have measurable disease (disease that has at least one lesion on imaging ≥ 10 mm x 10 mm) on imaging (gadolinium-enhanced MRI or if contraindicated, measurable CT, of the brain) prior to first study dose.
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Patients must be able to tolerate and consent for a lumbar puncture and/or have pre-existing placement of an Ommaya reservoir, unless clinically contraindicated.
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Patients must have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
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Demonstrate adequate bone marrow and organ function.
Exclusion Criteria:
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Patients are concurrently using other approved or investigational antineoplastic agents.
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Patients have an active concurrent malignancy requiring active therapy.
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Patients are allergic to components of the study drug.
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Patients have a known bleeding diathesis (eg, von Willebrand's disease) or hemophilia.
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Patients have significant abnormalities on screening electrocardiogram (ECG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening.
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Patients with the following will be excluded:
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A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval > 480 ms [CTCAE grade 2]) using Frederica's QT correction formula.
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A history of additional risk factors for Torsades de Pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
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The use of concomitant medications that prolong the QT/QTc interval.
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Patients are known to have a history of active or chronic infection with hepatitis C virus (HCV), hepatitis B virus (HBV), as determined by serologic tests.
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Known history of infection with human immunodeficiency virus (HIV).
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Patients are known to have an uncontrolled active infection.
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Patients have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment.
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Patients have a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the Investigator, could compromise the subject's safety or put the study outcomes at undue risk.
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Women who are pregnant or nursing (lactating).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Phoenix | Arizona | United States | 85054 |
| 2 | Mayo Clinic | Jacksonville | Florida | United States | 32224 |
| 3 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 4 | Linear Clinical Research | Nedlands | Western Australia | Australia | 6009 |
| 5 | Institut Curie Site Saint-Cloud | Saint-Cloud | Ile-de-France | France | 92210 |
| 6 | Middlemore Hospital | Papatoetoe | Auckland | New Zealand | 2025 |
Sponsors and Collaborators
- GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
Investigators
- Study Director: Renee Ward, MD, PhD, GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GB5121-2101