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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 2b, Open-label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of an Immunotherapeutic Treatment DPX-Survivac and Pembrolizumab, With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (VITALIZE)

Conditions
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Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: DPX-Survivac
* Drug: Pembrolizumab
* Drug: CPA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: DPX-Survivac, pembrolizumab, CPA<br>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. | Drug: DPX-Survivac<br>* SC injection on D7 and D28, then every 8 weeks<br>* Other names: maveropepimut-S;Drug: Pembrolizumab<br>* IV infusion every 3 weeks<br>* Other names: Keytruda;Drug: CPA<br>* 50 mg twice daily, week on then week off<br>* Other names: Cytoxan;|
| Experimental: Arm 2: DPX-Survivac, pembrolizumab<br>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. | Drug: DPX-Survivac<br>* SC injection on D7 and D28, then every 8 weeks<br>* Other names: maveropepimut-S;Drug: Pembrolizumab<br>* IV infusion every 3 weeks<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms |  | Approximately 24 months | 
| Duration of response (DOR) in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 24 months | 
| Time to response in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 24 months | 
| Progression-Free Survival in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 48 months | 
| Disease control rate (DCR) in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 24 months | 
| Complete response (CR) rate in each of the study arms | Centrally evaluated using Lugano (2014) | Approximately 24 months | 
| Changes in Patient Reported Outcomes using the FACT-Lym Assessment | The FACT-Lym is a validated questionnaire that consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General [FACT-G]) and a 15-item disease-specific questionnaire (Lymphoma Subscale). | Approximately 24 months | 
| Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment | The EQ-5D-5L is a 5-item measure that can be used to describe and value current overall health consisting of 5 items assessing mobility, self care, usual activities, pain/discomfort, and anxiety/depression. | Approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, Immunotherapy, T cell activation, Anti-PD-1, CAR-T ineligible, ASCT ineligible