cancer of the central nervous system lymphoma
Conditions
Interventions
Phase 1b (Dose Escalation and Expansion)
In Phase 1b Dose Escalation, the expected starting dose of GB5121 is 10 mg
twice daily (BID).
In the Phase 1b Expansion, the dose of GB5121 administered will
Sponsors
GB005, Inc., a wholly-owned subsidiary of Gossamer Bio, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Phase 1b Dose Escalation and Expansion: 1. Patients who are at least 18 years of age at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures. 2. Patients must have histologically/cytologically confirmed PCNSL, primary vitreoretinal lymphoma (PVRL), or CNS-only involvement of a systemic B-cell lymphoma. 3. All patients must have relapsed/refractory disease and must have received all possible standard-of-care CNS-directed treatment regimens or patients for which further standard-of-care treatment options are contraindicated or declined. 4. Patients must be able to tolerate gadolinium-enhanced MRI scans, or contrast-enhanced CT . 5. 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, 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). 6. Patients with parenchymal lesions must have measurable disease (disease that has at least one lesion >= 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. 7. 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. 8. Patients must have recovered to <= Grade 1 toxicity from prior therapy. 9. Patients, when available, should be able to submit at minimum 3 and up to 20 unstained formalin-fixed, paraffin-embedded (FFPE) slides from the initial tissue diagnosis, preferably prior to study enrollment. 10. Patients must have a performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 11. Demonstrate adequate bone marrow and organ function as defined in the protocol. All screening laboratories for organ functions should be performed within 14 days of initiating the study drug. 12. Female patients must be: a. Of non-childbearing potential: Evidence of post-menopausal status. Refer to Appendix 4 (Section 10.4) for definitions; or b. If of childbearing potential, patient must use a highly effective method of contraception for the duration of treatment and for at least 30 days following the last dose of GB5121. Refer to Appendix 4 (Section 10.4) for contraception guidance. c. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study drug. 13. Male patients who are not abstinent who are partners of women of childbearing potential must use 2 highly effective method of contraception throughout the entire study period. Refer to Appendix 4 (Section 10.4) for contraception guidance. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously). 14. Male and female patients must refrain from donating sperm or eggs from informed consent through at least 30 days after last dose of GB5121 for females and 90 days for males. 15.
Exclusion criteria
Exclusion criteria: Phase 1b Dose Escalation and Expansion: 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 (Section 5.1). 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: a. 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. b. A history of additional risk factors for Torsades de Pointes (eg, heart failure, hypokalemia, family history of long QT syndrome). c. The use of concomitant medications that prolong the QT/QTc interval (Section 10.6). 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 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 patient's safety or put the study outcomes at undue risk. 13. Patients have an inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (including malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease). 14. Women who are pregnant or nursing (lactating). 15. Patients have received chemotherapy, monoclonal antibodies, or targeted anticancer therapy within 8 mg/day of dexamethasone or the equivalent. 20. Patients underwent major systemic surgery within <= 2 weeks prior to enrolling in the study, or who has not recovered fr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b Dose Escalation Objectives • Incidence of AEs, DLTs, and SAEs • OBD and/or MTD and RP2D of GB5121 Phase 1b Expansion Objectives • Incidence of AEs and SAEs Phase 2 Objectives • ORR according to the IPCG criteria by Blinded Independent Central Review (BICR) Committee | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1b Expansion Objectives • ORR according to the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria by Investigator Assessment Phase 2 Objectives • Duration of Response (DOR) by BICR Committee | — |
Countries
Netherlands
Outcome results
None listed