Subjects are excluded from the study if any of the following criteria apply:

 

1. Primary CNS lymphoma or active secondary CNS involvement and/or lymphomatous meningitis. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS.

 

2. Chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of D0 or 5 half-lives whichever is shorter, except as noted:

a. Radiotherapy within 14 days of day 0. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.

b. Autologous stem cell transplant (ASCT) within ˂100 days prior to D0.
c. Chimeric antigen receptor T cell (CAR-T) therapy within ˂28 days prior to D0
All treatment related toxicities related to prior therapies must be recovered to < Grade 1 or baseline, except for organ function criteria mandated by the inclusion criteria. Subjects with Grade 2 alopecia, peripheral neuropathy endocrine-related AEs requiring treatment or hormone replacement are eligible.

3. The following prior medications/procedures are exclusionary.
a. Allogeneic stem cell transplant or allogeneic CAR-T therapy or solid organ transplant
b. Prior therapy with anti-survivin therapy
c. Anti-PD-1, anti-PD-L1, anti-PD-L2, or CTLA-4 agent
d. Chronic systemic steroid therapy (doses exceeding 10 mg daily prednisone equivalent) or other immunosuppressive therapy within 7 days of D0. Single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are permitted.
e. Prescribed or over-the-counter probiotic treatments
f. Live-attenuated vaccine within 30 days of planned start of study therapy

4. Disorders that might interfere with study treatment including:
a. History of (non-infectious) pneumonitis that required steroids or current pneumonitis
b. Unable to swallow tablets, malabsorption syndrome, short-gut syndrome, gastroparesis or any other gastrointestinal disease or dysfunction (e.g., nausea/vomiting/diarrhea that is CTCAE ≥ Grade 2) that could interfere with absorption of study treatment
c. Acute or chronic skin, microvascular disorders, and/or edema or lymphedema that could interfere with subcutaneous injection of DPX-Survivac or subsequent assessment of potential skin reactions.

5. Diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted.

6. Clinically severe cardiovascular disease (e.g., NYHA Class III or IV CHF, uncontrolled angina; history of myocardial infarction within 6 months or unstable angina or stroke within 30 days of study entry; uncontrolled hypertension; or clinically significant arrhythmias not controlled by medication).

7. Uncontrolled significant active infections.
a. Subjects who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Note: Subjects should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
b. Subjects with HCV are eligible if HCV viral load is undetectable at screening. Note: Subjects must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
c. HIV infected subjects must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease defined as:
i. Subjects on ART must have a CD4+ T-cell count >350 cells/mm3 at time of screening
ii. Subjects on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening
iii. Subjects on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to D0.

iv. HIV-infected subjects cannot have a history of Kaposi sarcoma and/or Multicentric Castleman Disease.

8. Prior history of malignancy other than eligible lymphoma sub-types, unless the subject has been free of the disease for ≥ 2 years prior to the start of study treatment. Subjects with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, and organ-confined prostate cancer with no evidence of progressive disease.

9. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.

10. Known intolerance to DPX-Survivac and/or CPA, or chemical derivatives or any of the excipients.

11. A WOCBP who has a positive pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

12. Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).

13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.