DPX-Survivac + Pembrolizumab for Lymphoma
(VITALIZE Trial)
Recruiting in Palo Alto (17 mi)
+43 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)
Must not be taking: Chemotherapy, Immunotherapy
Disqualifiers: CNS lymphoma, Autoimmune, Infections, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot have had chemotherapy, immunotherapy, major surgery, or investigational treatments within 28 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug pembrolizumab for lymphoma?
Is the combination of DPX-Survivac and Pembrolizumab generally safe for humans?
Pembrolizumab, a part of the treatment, has been studied in various trials and is generally considered safe, though it can cause rare immune-related side effects like type 1 diabetes in 0.2% of cases. In nonhuman primate studies, pembrolizumab showed no significant toxic effects, supporting its safety profile in humans.12678
What makes the drug DPX-Survivac + Pembrolizumab unique for treating lymphoma?
The combination of DPX-Survivac and Pembrolizumab is unique because it combines an immune-boosting vaccine (DPX-Survivac) with an immune checkpoint inhibitor (Pembrolizumab) that blocks PD-1, a protein that helps cancer cells evade the immune system. This approach aims to enhance the body's immune response against lymphoma, potentially offering a novel treatment option compared to traditional therapies.235910
Eligibility Criteria
Adults over 18 with relapsed/refractory Diffuse Large B-Cell Lymphoma (DLBCL) who've had at least two prior treatments, including an anthracycline and rituximab. They must have a measurable lesion, life expectancy over 3 months, decent performance status, and be ineligible for or failed ASCT or CAR-T therapy. Excludes those with recent transplants, active autoimmune diseases requiring treatment within the past 2 years, recent radiotherapy or other therapies before the trial start.Inclusion Criteria
Have at least one bi-dimensionally measurable lesion per Lugano (2014)
Meet protocol-specified laboratory requirements
I cannot have stem cell or CAR-T therapy due to ineligibility or past treatment failure.
See 6 more
Exclusion Criteria
I have not had CAR-T therapy in the last 28 days.
I do not have any serious active infections, except for controlled Hepatitis B, C, or HIV.
I have not had radiotherapy in the last 14 days.
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive DPX-Survivac and pembrolizumab, with or without CPA. DPX-Survivac is administered as two 0.5 mL doses 3 weeks apart, followed by up to twelve 0.1 mL doses 8 weeks apart. Pembrolizumab is administered every 3 weeks. CPA is administered intermittently for Arm 1.
Approximately 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Approximately 24 months
Long-term Follow-up
Participants are monitored for progression-free survival and other long-term outcomes
Approximately 48 months
Treatment Details
Interventions
- Cyclophosphamide (Alkylating agents)
- DPX-Survivac (Cancer Vaccine)
- Pembrolizumab (Checkpoint Inhibitor)
Trial OverviewThis Phase 2b study is testing DPX-Survivac and pembrolizumab's safety and effectiveness in treating DLBCL when given alone or combined with low-dose cyclophosphamide (CPA). Participants are randomly assigned to receive these interventions to see how well they work against this type of lymphoma.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm 2: DPX-Survivac, pembrolizumabExperimental Treatment2 Interventions
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.
Group II: Arm 1: DPX-Survivac, pembrolizumab, CPAExperimental Treatment3 Interventions
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 is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as DPX-Survivac for:
- None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma
🇪🇺 Approved in European Union as DPX-Survivac for:
- None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma
🇨🇦 Approved in Canada as DPX-Survivac for:
- None approved yet; under investigation for various cancers including ovarian cancer and diffuse large B-cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Saskatchewan Cancer AgencySaskatoon, Canada
Oncology Hematology West, PC dba Nebraska Cancer SpecialistsOmaha, NE
Blood and Marrow Transplant Group of GeorgiaAtlanta, GA
Reading Hospital - McGlinn Cancer InstituteWest Reading, PA
More Trial Locations
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Who Is Running the Clinical Trial?
ImmunoVaccine Technologies, Inc. (IMV Inc.)Lead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2020]Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer. In this review we will summarize the data for efficacy and toxicity for these two agents. We conclude that they represent two valuable but interchangeable alternatives to target their approved indications. We will discuss how this can help global payers seeking to contain the cost of cancer therapeutics that continues to spiral out of control.
Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]Pembrolizumab has shown significantly better efficacy than platinum doublet chemotherapy in patients with programmed cell death ligand 1 (PD-L1) strongly positive (tumor proportion score ≥ 50%) non-small-cell lung cancer (NSCLC). However, the predictors of response to pembrolizumab have not yet been fully elucidated for patients with PD-L1 strongly positive NSCLC.
Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]Introduction: Pembrolizumab is a novel monoclonal antibody that targets the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Pembrolizumab has shown significant clinical efficacy in Hodgkin Lymphoma (HL), but results in non Hodgkin Lymphoma (NHL) are mixed. Some NHL subtypes, which share certain genetic features with HL, such as alterations in chromosome 9p24.1 and expression of PD-L1, have shown promising responses in early phase trials. Areas covered: In this review, we provide an overview of pembrolizumab as a compound, and present the available clinical efficacy and safety data in the treatment of diffuse large B cell lymphomas. Expert opinion: Current early phase data suggest that single agent pembrolizumab in NHL demonstrates both efficacy and a favorable safety profile. However, it is anticipated that future treatment strategies will be biomarker-driven and incorporate pembrolizumab into combination therapies with chemotherapy and/or immunotherapy agents.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection. Pembrolizumab binds to human and cynomolgus monkey PD-1 with picomolar affinity and blocks the binding of human and cynomolgus monkey PD-1 to PD-L1 and PD-L2 with comparable potency. Pembrolizumab binds both the C'D and FG loops of PD-1. Pembrolizumab overcomes human and cynomolgus monkey PD-L1-mediated immune suppression in T-cell cultures by enhancing IL2 production following staphylococcal enterotoxin B stimulation of healthy donor and cancer patient cells, and IFNγ production in human primary tumor histoculture. Ex vivo and in vitro studies with human and primate T cells show that pembrolizumab enhances antigen-specific T-cell IFNγ and IL2 production. Pembrolizumab does not mediate FcR or complement-driven effector function against PD-1-expressing cells. Pembrolizumab displays dose-dependent clearance and half-life in cynomolgus monkey pharmacokinetic and toxicokinetic studies typical for human IgG4 antibodies. In nonhuman primate toxicology studies, no findings of toxicologic significance were observed. The preclinical data for pembrolizumab are consistent with the clinical anticancer activity and safety that has been demonstrated in human clinical trials.
Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. [2023]In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population.
Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]Pembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment.
Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. [2022]Treatment options for relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD-1 ligand overexpression, potentially making PMBCL particularly susceptible to PD-1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti-PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial. At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of therapy) had been enrolled and treated, of whom 17 were included in the efficacy analyses. Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow-up of 11.3 months, median duration of response was not reached. Two patients reached the maximum 2-year treatment duration and remain in remission. Median overall survival was not reached for treated patients overall; all responders were still alive at data cutoff. These results in heavily pretreated rrPMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor activity. This trial was registered at www.clinicaltrials.gov as #NCT01953692.