DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.

This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL. The study will enroll up to 102 subjects. Eligible subjects will be randomized (1:1) to receive: * Arm 1: DPX-Survivac, pembrolizumab and intermittent, low-dose CPA; or, * Arm 2: DPX-Survivac and pembrolizumab All subjects will receive two 0.5 mL doses of DPX-Survivac 3 weeks apart on day 7 (D7) and D28 followed by up to twelve 0.1 mL doses of DPX-Survivac, 8 weeks apart (Q8W). All subjects will receive pembrolizumab intravenously (IV) at a flat dose of 200 mg starting at D7 and on day 1 of each 3-week cycle thereafter (i.e., D28, D49, D70 etc.) (Q3W). For subjects randomized to Arm 1, intermittent oral CPA at a dose of 50 mg twice a day (BID) is administered from D0 to D6 (7 days) followed by 7 days off. This 14-day cycle of "7 days on and 7 days off" will be repeated until the end of study treatment.

Key Inclusion Criteria: * Adults ≥ 18 years of age who are willing and able to provide written informed consent * Have an ECOG performance status of ≤ 1. Subjects with an ECOG performance status of 2 may be enrolled with Medical Monitor approval. * Pathologically confirmed diagnosis of DLBCL, as defined by the 2016 World Health Organization classification including DLBCL NOS high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, Epstein-barr virus (EBV) positive DLBCL, and T cell rich B cell lymphoma (TCRBCL). Subjects with DLBCL transformed from indolent lymphoma (except for Richter's transformation) are eligible. * Subjects must have progressive disease following at least two (2) lines of prior systemic therapy for DLBCL; prior treatment must have included an anthracycline and rituximab (or another CD20-targeted agent). * Subjects must have failed or be ineligible for ASCT or CAR-T * Have at least one bi-dimensionally measurable lesion per Lugano (2014) * Willing to provide pre-treatment and on-treatment tumor biopsy tissue. * Meet protocol-specified laboratory requirements * Life expectancy \> 3 months. Key Exclusion Criteria: * Primary CNS lymphoma or active secondary CNS involvement and/or lymphomatous meningitis * Chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of D0 or 5 half-lives, whichever is shorter * Radiotherapy within 14 days of day 0 * Autologous stem cell transplant (ASCT) within ˂100 days prior to D0 * Chimeric antigen receptor T cell (CAR-T) therapy within ˂28 days prior to D0 * Diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years * Uncontrolled significant active infections (controlled Hepatitis B, Hepatitis C, or HIV may be eligible) * 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