Inclusion Criteria:

1. Males and females greater than or equal to 18 years of age

2. Life expectancy of at least 3 months

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable).
Cerebral biopsies are not required if imaging reveals typical images of PCNSL.

1. Patients with parenchymal lesions must have unequivocal evidence (e.g., presence
of at least 1 bi-dimensionally measurable target lesion on brain magnetic
resonance imaging (MRI) or head CT or a new lesion with CSF involvement) of
disease progression on imaging within 28 days prior to Cycle 1 Day 1.

2. For patients with leptomeningeal disease only, CSF cytology must document
lymphoma cells or monotypic cells on flowcytometry, and/or imaging findings
consistent with CSF disease within 28 days prior to Cycle 1 Day 1 (at the
discretion of the Investigator).

Exclusion Criteria for Part B - PCNSL Expansion Cohorts of Combination Therapy:

1. Patients with only intraocular PCNSL without brain lesion or CSF involvement or T-cell
lymphoma or systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS

2. Prior history of malignancies other than lymphoma (except for basal cell or squamous
cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior
history of systemic lymphoma, unless the patient has been free of the disease for ≥ 3
years.

3. Active malignancy other than PCNSL requiring systemic therapy

4. History of Grade ≥ 3 rhabdomyolysis without complete recovery

5. Patient has received external beam radiation therapy to the CNS within 28 days prior
to Cycle 1 Day 1.

6. Prior investigational drugs (including treatment in clinical research, unapproved
combination products, and new dosage forms) within 28 days or 5 half-lives, whichever
is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant
(HSCT) within 60 days prior to C1D1; or clinically significant graft-versus-host
disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior
to Screening Note: The use of a stable or tapering dose of immunosuppressive therapy
post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor
Medical Monitor approval

7. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug
therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to
Cycle 1 Day 1 (with the exception of ibrutinib, which may be continued as part of this
study without interruption)

8. Prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any
excipients.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/13/2024. Questions regarding updates should be directed to the study team contact