Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B-cell Lymphoma
Conditions
Keywords
Immunotherapy, T cell activation, DLBCL, Anti-PD-1, CAR-T ineligible, ASCT ineligible
Brief summary
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
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.
Interventions
DRUGDPX-Survivac
SC injection on D7 and D28, then every 8 weeks
DRUGPembrolizumab
IV infusion every 3 weeks
DRUGCPA
50 mg twice daily, week on then week off
Sponsors
Merck Sharp & Dohme LLC
ImmunoVaccine Technologies, Inc. (IMV Inc.)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) in each of the study arms | Approximately 24 months | Centrally evaluated using Lugano (2014) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) in each of the study arms | Approximately 24 months | Centrally evaluated using Lugano (2014) |
| Time to response in each of the study arms | Approximately 24 months | Centrally evaluated using Lugano (2014) |
| Progression-Free Survival in each of the study arms | Approximately 48 months | Centrally evaluated using Lugano (2014) |
| Disease control rate (DCR) in each of the study arms | Approximately 24 months | Centrally evaluated using Lugano (2014) |
| Complete response (CR) rate in each of the study arms | Approximately 24 months | Centrally evaluated using Lugano (2014) |
| Changes in Patient Reported Outcomes using the FACT-Lym Assessment | Approximately 24 months | 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). |
| Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment | Approximately 24 months | 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. |
| Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms | Approximately 24 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) in each of the study arms | Approximately 48 months | — |
| Time to second objective disease progression (PFS2) in each of the study arms | Approximately 48 months | — |
| Cell mediated immune response | Approximately 24 months | — |
| Changes in immune cell infiltration in tumor biopsies | Approximately 24 months | — |
| Time to next treatment (TTNT) in each of the study arms | Approximately 48 months | — |
| Objective Response Rate (ORR) based on PD-L1 expression | Approximately 24 months | Centrally evaluated using Lugano (2014) and central assessment of PD-L1 using validated 22C3 assay |
Countries
Australia, Canada, France, Hungary, New Zealand, Poland, Romania, Serbia, Spain, United States
Outcome results
None listed