This phase I trial tests the safety, side effects, and best dose of nivolumab in combination with ASTX727 in treating B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. ASTX727 consists of the combination of decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving nivolumab in combination with ASTX727 may shrink and stabilize cancer.
Dose Escalation: Histologically confirmed relapsed or refractory B cell lymphoma (non-Hodgkin lymphoma [NHL] or Hodgkin lymphoma [HL])
Dose Expansion: Patients must have histologically confirmed relapsed or refractory DLBCL or HL
Patients with DLBCL must have failed at least first line chemotherapy and must be transplant ineligible (either secondary to performance status or lack of adequate disease control or patient preference). Patients may be relapsed after autologous or allogeneic stem cell transplant (SCT), or after chimeric antigen receptor (CAR)-T cell therapy
In dose escalation patients with HL or B cell NHL other than DLBCL must have relapsed after at least 2 lines of therapy and have no other curative options left. HL patients must be brentuximab vedotin refractory or intolerant. In dose expansion, patients with classic HL must have relapsed after at least 2 lines of therapy, and had autologous stem cell transplantation (ASCT), be ineligible for ASCT, or have refused ASCT. Prior treatment with checkpoint inhibitor is allowed
Repeat imaging demonstrates no new sites of bone metastases
The lesion being considered for palliative radiation is not a target lesion
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who have had prior treatment with anti-PD-1/PD-L1 inhibitors or anti CTLA4 antibodies and were permanently discontinued from further treatment because of an adverse event. All other prior therapies are permissible. Prior checkpoint inhibitor therapy is allowed if there was no discontinuation due to adverse event