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

Immunovaccine

Status and phase: Enrolling; Phase 2

Conditions: Refractory Diffuse Large B-cell Lymphoma; Relapsed Diffuse Large B-cell Lymphoma

Treatments: Drug: DPX-Survivac; Drug: Pembrolizumab; Drug: CPA

Study type: Interventional

Funder types: Industry

Identifiers

NCT04920617

P1605-SUR-D23

KEYNOTE-C54 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 102 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Arm 1: DPX-Survivac, pembrolizumab, CPA

Experimental group

Description:

Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0.

Treatment:

Drug: CPA

Drug: Pembrolizumab

Drug: DPX-Survivac

Arm 2: DPX-Survivac, pembrolizumab

Experimental group

Description:

Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. Subjects randomized to Arm 2 will not receive CPA.

Treatment:

Drug: Pembrolizumab

Drug: DPX-Survivac