Description:
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of
DPX-Survivac alone or in combination with pembrolizumab, with and without low-dose
cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
Title
- Brief Title: DPX-Survivac, Alone or in Combination With Pembrolizumab, With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Official Title: A Phase 2b, Open-label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of an Immunotherapeutic Treatment DPX-Survivac, Alone or in Combination With Pembrolizumab, With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
P1605-SUR-D23
- SECONDARY ID:
KEYNOTE-C54
- NCT ID:
NCT04920617
Conditions
- Relapsed Diffuse Large B-cell Lymphoma
- Refractory Diffuse Large B-cell Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| DPX-Survivac | maveropepimut-S | Arm 1: DPX-Survivac, pembrolizumab, CPA |
| Pembrolizumab | MK-3475, Keytruda | Arm 1: DPX-Survivac, pembrolizumab, CPA |
| CPA | Intermittent, low-dose cyclophosphamide, Procytox, Cytoxan | Arm 1: DPX-Survivac, pembrolizumab, CPA |
Purpose
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of
DPX-Survivac alone or in combination with pembrolizumab, with and without low-dose
cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
Detailed Description
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of
DPX-Survivac alone or in combination with pembrolizumab, with and without low-dose
cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
The study will enroll up to 152 subjects. Eligible subjects will be randomized (1:1:1) to
receive:
- Arm 1: DPX-Survivac, pembrolizumab and intermittent, low-dose CPA; or,
- Arm 2: DPX-Survivac and pembrolizumab; or,
- Arm 3: DPX-Survivac
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).
Subject randomized to Arm 1 or 2 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm 1: DPX-Survivac, pembrolizumab, CPA | Experimental | 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. | - DPX-Survivac
- Pembrolizumab
- CPA
|
| Arm 2: DPX-Survivac, pembrolizumab | Experimental | 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. | - DPX-Survivac
- Pembrolizumab
|
| Arm 3: DPX-Survivac | Experimental | 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. | |
Eligibility 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.
- 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; 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
- Primary refractory disease, defined as: documented persistent disease at the
completion of first-line therapy, or progressive disease within 3 months of completion
of treatment
- 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) or chimeric antigen receptor T cell (CAR-T)
therapy within 100 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective response rate (ORR) in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
Secondary Outcome Measures
| Measure: | Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response (DOR) in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
| Measure: | Time to response in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
| Measure: | Progression-Free Survival in each of the study arms |
| Time Frame: | Approximately 48 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
| Measure: | Disease control rate (DCR) in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
| Measure: | Complete response (CR) rate in each of the study arms |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | Centrally evaluated using Lugano (2014) |
| Measure: | Changes in Patient Reported Outcomes using the FACT-Lym Assessment |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment |
| Time Frame: | Approximately 24 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | ImmunoVaccine Technologies, Inc. (IMV Inc.) |
Trial Keywords
- Immunotherapy
- T cell activation
- DLBCL
- Anti-PD-1
- CAR-T ineligible
- ASCT ineligible
Last Updated
August 6, 2021
