A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

Inclusion Criteria:

Males and females greater than or equal to 18 years of age
Life expectancy of at least 3 months
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

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

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.
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

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
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.
Active malignancy other than PCNSL requiring systemic therapy
History of Grade ≥ 3 rhabdomyolysis without complete recovery
Patient has received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
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
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)
Prior history of hypersensitivity or anaphylaxis to emavusertib or ibrutinib or any excipients.