Overview
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.
Description
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.
Eligibility
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