GB5121 in Adult Patients With Relapsed/Refractory CNS Lymphoma (STAR CNS)

• ClinicalTrials.gov Identifier: NCT05242146
• Recruitment Status: Active, not recruiting
• First Posted: February 16, 2022
• Last Update Posted: April 20, 2023
• Sponsor: GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Information provided by (Responsible Party): Gossamer Bio Inc. ( GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. )

Tracking Information

• First Submitted Date: January 31, 2022
• First Posted Date: February 16, 2022
• Last Update Posted Date: April 20, 2023
• Actual Study Start Date: May 24, 2022
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2022)

• Phase 1b Dose Escalation - Incidence of Adverse Events [ Time Frame: From first dose until 28 days after the last dose of GB5121 ]
• Phase 1b Dose Escalation - Dose Limiting Toxicity(ies) [ Time Frame: From Cycle 1, Day 1 through Cycle 1, Day 28 inclusive, Each Cycle=28 days ]
• Phase 1b Dose Escalation - Serious Adverse Events [ Time Frame: 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 [ Time Frame: From first dose up to approximately 36 months ]
• Phase 1b Dose Expansion - Incidence of Adverse Events [ Time Frame: From first dose until 28 days after the last dose of GB5121 ]
• Phase 1b Dose Expansion - Serious Adverse Events [ Time Frame: 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) [ Time Frame: From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months ]

Original Primary Outcome Measures (submitted: February 15, 2022)

• Phase 1b Dose Escalation - Incidence of Adverse Events [ Time Frame: From first dose until 30 days after of the last dose of GB5121 ]
• Phase 1b Dose Escalation - Dose Limiting Toxicity(ies) [ Time Frame: From Cycle 1, Day 1 through Cycle 1, Day 28 inclusive, Each Cycle=28 days ]
• Phase 1b Dose Escalation - Serious Adverse Events [ Time Frame: From consent until 28 days after the last dose ]
• Phase 1b Dose Expansion - Incidence of Adverse Events [ Time Frame: From first dose until 30 days after of the last dose of GB5121 ]
• Phase 1b Dose Expansion - Serious Adverse Events [ Time Frame: From consent until 28 days after the last dose ]
• Phase 1b Dose Expansion - Maximum Tolerated Dose and/or Optimal Biologic Dose and Recommended Phase 2 Dose [ Time Frame: From first dose up to approximately 36 months ]
• Phase 2 - Objective Response Rate According to IPCG Criteria by Blinded Independent Central Review Committee (IPCG) [ Time Frame: From Study Day 1 until disease progression assessed by the Investigator per IPCG criteria, unacceptable toxicity, or discontinuation, up to approximately 36 months ]

Current Secondary Outcome Measures (submitted: August 31, 2022)

• Phase 1b Dose Expansion - Objective Response Rate According to IPCG Criteria by Investigator Assessment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From Study Day 1 until Week 24 ]
• Phase 2 - Median Overall Survival [ Time Frame: From Study Day 1 until death, unacceptable toxicity, or discontinuation, up to approximately 36 months ]
• Phase 2 - Incidence of Adverse Events [ Time Frame: From first dose until 28 days after the last dose of GB5121 ]
• Phase 2 - Incidence of Serious Adverse Events [ Time Frame: From consent until 28 days after the last dose of GB5121 ]

Original Secondary Outcome Measures (submitted: February 15, 2022)

• Phase 1b Dose Expansion - Objective Response Rate According to IPCG Criteria by Investigator Assessment [ Time Frame: 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 Blinded Independent Central Review Committee [ Time Frame: 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 Blinded Independent Central Review Committee [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From Study Day 1 until Week 24 ]
• Phase 2 - Overall Survival [ Time Frame: 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 - Incidence of Adverse Events [ Time Frame: From first dose until 30 days after of the last dose of GB5121 ]
• Phase 2 - Incidence of Serious Adverse Events [ Time Frame: From consent until 28 days after the last dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GB5121 in Adult Patients With Relapsed/Refractory CNS Lymphoma
• Official Title: A Phase 1b/2, Open-label Dose Escalation With Expansion Study of GB5121 in Adult Patients With Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma or Primary Vitreoretinal Lymphoma, With a Phase 2 Open-label Single Dose Level Study of GB5121 in Adult Patients With Relapsed/ Refractory Primary Central Nervous System Lymphoma
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: CNS Lymphoma

Intervention

Drug: GB5121

Capsule containing GB5121

Study Arms

Experimental: GB5121

GB5121 orally twice per day (BID)

Intervention: Drug: GB5121

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 1, 2022): 158
• Original Estimated Enrollment (submitted: February 15, 2022): 128
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients must have histologically/cytologically confirmed primary central nervous system lymphoma (PCNSL), primary vitreoretinal lymphoma (PVRL), or CNS-only involvement of a systemic B-cell lymphoma.
2. All patients must have relapsed/refractory disease and must have received all possible standard-of-care CNS-directed therapy treatment regimens or patients for which further standard-of-care treatment options are contraindicated or declined.
3. Patients must be able to tolerate gadolinium-enhanced magnetic resonance imaging (MRI) scans, or contrast-enhanced computed tomography (CT).
4. Patients with parenchymal lesions must have baseline imaging (gadolinium-enhanced MRI or if contraindicated, contrast-enhanced 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 leptomeningeal disease after informed consent and prior to first study dose (at the discretion of the Investigator).
5. Patients with parenchymal lesions must have measurable disease (disease that has at least one lesion on imaging ≥ 10 mm in the longest diameter) on imaging (gadolinium-enhanced MRI or if contraindicated, contrast-enhanced CT, of the brain) prior to first study dose.
6. 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.
7. Patients must have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
8. Demonstrate adequate bone marrow and organ function.

Exclusion Criteria:

1. Patients are concurrently using other approved or investigational antineoplastic agents.
2. Patients have an active concurrent malignancy requiring active therapy.
3. Patients are allergic to components of the study drug.
4. Patients have a known bleeding diathesis (eg, von Willebrand's disease) or hemophilia.
5. Patients who require therapeutic anticoagulation, including dual antiplatelet agents. Patients who have received therapeutic anticoagulation, including dual antiplatelet agents, within 5 half-lives of the anticoagulant or 14 days, whichever is longer, prior to starting the study drug. Patients who require the use of antiplatelet agents should be discussed with the Sponsor's Medical Monitor.
6. 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.

7. Patients with any of the following will be excluded:

   1. 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.
   2. A history of additional risk factors for Torsades de Pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
   3. The use of concomitant medications that prolong the QT/QTc interval.
8. 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.
9. Known history of infection with human immunodeficiency virus (HIV).
10. Patients are known to have an uncontrolled active infection.
11. Patients have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment.
12. 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.
13. Women who are pregnant or nursing (lactating).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Israel, New Zealand, United States

Administrative Information

• NCT Number: NCT05242146
• Other Study ID Numbers: GB5121-2101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gossamer Bio Inc. ( GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Renee Ward, MD, PhD; GB005, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.

• PRS Account: Gossamer Bio Inc.
• Verification Date: April 2023