DPX-Survivac and Checkpoint Inhibitor in DLBCL

Inclusion Criteria

In order to be eligible for participation in this trial, the subject must:

• Be willing and able to provide written informed consent/assent for the trial.
• Male or female 18+ years of age on day of signing informed consent and of any racial or ethnic group
• Has:

A. histologically proven DLBCL with recurrence after first, second or tertiary treatment regimens for DLBCL or,

B. evidence of transformed lymphoma with past history of indolent lymphoma with current biopsy showing DLBCL) or,

C. double hit or high grade lymphomas, including Burkitts lymphoma and High Grade B-Cell lymphoma unclassifiable (with features intermediate between Burkitts and diffuse large B cell lymphoma)

• Has had:

A. recurrence requiring therapy at least 90 days post aggressive first line combination chemotherapy (e.g. RCHOP, Hyper-CVAD or other aggressive "curative" combination), autologous stem cell transplantation (ASCT), CART therapy, or aggressive second line combination therapy or,

B. partial response or measureable disease after first line therapy (who are not candidates for ASCT) or after second or third line therapy without disease progression or,

C. recurrence any time after non-aggressive combination or single agent therapy with or without Rituximab (i.e. CVP, CHL or, VP16) for first, second or third line disease or,

D. for subjects with transformed lymphoma, a treatment for indolent lymphoma within the last 2 years

• Have at least one measurable site of disease based on Cheson Criteria using standard CT imaging.
• Be willing to provide tissue from a newly obtained (up to 3 months + 7 days prior to Study Day 0) biopsy of a tumour lesion. If this is not available, the patient must be willing to undergo a core biopsy prior to starting treatment. They must also be willing to provide an on-treatment biopsy.
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 2, within 48 hours prior to receiving the first dose of study medication (SD0). Patients with abnormal liver enzymes of up to 5 times the upper limit of normal and/or reduced GFR of 50-100% normal range can be considered for enrolment if the alteration is due to lymphoma.
• Previous localized surgery, radiotherapy, chemotherapy, and immunotherapy more than 21 days prior to SD0. Cyclophosphamide, up to 100 mg/day, may be administered until SD-1 for subjects already receiving as a single agent therapy.
• A life expectancy > 6 months.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 48 hours prior to receiving the first dose of study medication (SD0). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through to 120 days from the last dose of study medication.
• Ability to comply with protocol requirements.

Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 21 days of the first dose of treatment (SD0).
• Patients eligible for possible curative therapies such as ASCT.
• LDH greater than 5 times the upper limit of normal.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 35 days