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

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. Patients provide written informed consent for the study which includes
compliance with the requirements and restrictions listed in the ICF and in this
protocol.

Phase 2: criteria specific to phase 2, the remaining criteria are identical
with phase1b, criteria 7 is not applicable
2. Patients with histologically/cytologically confirmed PCNSL.
5. Patients with parenchymal lesions must have baseline imaging
(gadolinium-enhanced MRI or if contraindicated, contrast-enhanced CT, of the
brain) after informed consent and prior to first study drug dose. For subjects
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).

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 <= 2 weeks or 5 half-lives, whichever is longer, prior
to starting the study drug, or the patient has not recovered from the side
effects of such therapy.
16. Patients have received external beam radiation therapy (WBRT, SRS) to the
CNS within 21 days of the first dose of the study drug.
17. Patients do not meet prior and concomitant medication criteria (Section
5.5.3).
18. Patients have previously received a BTK inhibitor. Patients who have
previously received a BTK inhibitor, but discontinued therapy for reasons other
than disease progression are eligible.
19. Patients require > 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 from the side effects of such
surgery, or who plans to have surgery within 2 weeks of the first dose of the
study drug.
21. Patients have undergone prior allogeneic stem cell transplant (autologous
stem cell transplant is NOT an exclusion).
22. CAR-T (chimeric antigen receptor T cell) therapy within 60 days of the
first dose of GB5121 or ongoing immunosuppressive therapy post CAR-T therapy at
the time of screening, clinically significant graftversus-host disease (GVHD),
or need for anticytokine therapy for toxicity from CAR-T therapy; residual
symptoms of neurotoxicity > Grade 1 from CAR-T therapy.
23. Received a live vaccine within 30 days prior to the first dose of study
drug. Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,
Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed;
however, intranasal influenza vaccines (eg, FluMist®) are live attenuated
vaccines and are not allowed. Approved COVID-19 vaccines are allowed (Emergency
Use Authorization and/or full approval).
24. Currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 2 weeks
prior to the first dose of study drug.

Phase 2: criteria specific to phase 2, the remaining criteria are identical
with phase1b
1. Patients with SCNSL or PVRL.