Pembrolizumab, Ibrutinib and Rituximab in PCNSL

Must have received: CNS-directed therapy

Subjects with pathologically confirmed PCNSL who progressed after CNS-directed therapy, primary refractory disease and relapsed disease are allowed.

Cannot have received: anti-PD-1/PD-L1/PD-L2 or co-inhibitory T-cell receptor therapy

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40,CD137)

Cannot have received: BTK inhibitor (ibrutinib)

Exception: patient who have previously received BTK inhibitor but not progressed while on it are allowed

Previously progressed on ibrutinib or other BTK inhibitor use (patient who have previously received BTK inhibitor but not progressed while on it are allowed)

Cannot have received: systemic anti-cancer therapy

Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to dosing. OR 5 half-lives, whichever is shorter

Cannot have received: radiotherapy to CNS disease

Exception: A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease

Has received prior radiotherapy to CNS disease within 2 weeks of start of study treatment

Cannot have received: allogeneic stem cell transplant

Patients who have undergone prior allogeneic stem cell transplant