DPX-Survivac + Pembrolizumab for Lymphoma

(VITALIZE Trial)

Recruiting at 46 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: CNS lymphoma, Autoimmune, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 24 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the combination of two treatments, DPX-Survivac (also known as Maveropepimut-S) and pembrolizumab, to assess their effectiveness and safety for individuals with diffuse large B-cell lymphoma (DLBCL) that has recurred or not responded to treatment. Some participants will also receive a low dose of cyclophosphamide, a chemotherapy drug, to determine if it enhances the treatment's effectiveness. This trial suits those who have tried at least two other treatments for DLBCL, have a type that has progressed, and have not succeeded with stem cell or CAR-T therapies. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the combination of DPX-Survivac and pembrolizumab is well-tolerated, meaning people generally handle these treatments without serious problems. Another study found that using DPX-Survivac with pembrolizumab and cyclophosphamide (a chemotherapy drug) was also well-tolerated in people with recurring ovarian cancer. This suggests that adding cyclophosphamide might not introduce significant new safety concerns.

However, it's important to note that this trial is in Phase 2, which is still early in testing. This phase usually focuses on evaluating treatment efficacy and safety. So far, the combination treatments appear manageable for most people, but some risks might not yet be fully understood. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of DPX-Survivac and Pembrolizumab for lymphoma because it represents a novel approach compared to current standard treatments like chemotherapy and monoclonal antibodies. DPX-Survivac is a cancer vaccine that targets the survivin protein, which is crucial for cancer cell survival and is often overexpressed in tumors. Pembrolizumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. In Arm 1 of the study, the addition of CPA (cyclophosphamide) may further enhance the immune response by reducing immune suppression. This multi-pronged strategy offers a potentially more targeted and robust attack on lymphoma cells, raising hopes for improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for relapsed or refractory DLBCL?

Research shows that using DPX-Survivac with pembrolizumab may help treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Studies have found that this combination can enhance the immune system's ability to identify and attack cancer cells. In this trial, participants in Arm 1 will receive DPX-Survivac, pembrolizumab, and a small dose of cyclophosphamide (CPA), which the Spirel study suggested might enhance treatment effectiveness. Participants in Arm 2 will receive DPX-Survivac and pembrolizumab without CPA. Early trial results showed positive responses in patients using the DPX-Survivac and pembrolizumab combination, with or without CPA. This suggests that this treatment could be effective for DLBCL when other treatments have not succeeded. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• DPX-Survivac
• Pembrolizumab

Trial Overview This 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.

How Is the Trial Designed?

Group I: Arm 2: DPX-Survivac, pembrolizumab Experimental Treatment 2 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, CPA Experimental Treatment 3 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

Who Is Running the Clinical Trial?

ImmunoVaccine Technologies, Inc. (IMV Inc.)

Lead Sponsor

Trials

11

Recruited

580+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the KEYNOTE-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

In the KEYNOTE-355 trial, patients with previously untreated metastatic triple-negative breast cancer (mTNBC) who received pembrolizumab combined with chemotherapy experienced a significant improvement in quality-adjusted survival, gaining an average of 3.7 months more time without symptoms or treatment toxicity compared to those receiving chemotherapy alone.

The benefits of pembrolizumab plus chemotherapy increased over time, with a 20% relative gain in quality-adjusted survival at a maximum follow-up of 52 months, indicating both efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1. Huang, M., O'Shaughnessy, J., Haiderali, A., et al.[2023]

In a study involving 18 patients with relapsed/refractory primary mediastinal large B-cell lymphoma, pembrolizumab (an anti-PD-1 antibody) showed a promising overall response rate of 41%, with 61% of patients experiencing manageable drug-related adverse events, mostly mild (grade 1-2).

The treatment demonstrated significant antitumor activity, as 81% of patients had decreases in target lesions, and all responders were alive at the time of data cutoff, indicating potential for long-term remission in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Zinzani, PL., Ribrag, V., Moskowitz, CH., et al.[2022]

In a study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04920617

NCT04920617 | DPX-Survivac and Pembrolizumab With ... 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 ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT04920617

DPX-Survivac and Pembrolizumab With and Without ... | "IMV Inc....announced positive preliminary data from the VITALIZE Phase 2B trial evaluating its lead DPX product, maveropepimut-S ('MVP-S'), in combination ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39866944/

Characteristics of relapsed/refractory diffuse large B-cell ... The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118713001

Clinical Effectiveness of Combination Immunotherapy DPX ... Clinical effectiveness of combination immunotherapy DPX-Survivac, low dose cyclophosphamide, and pembrolizumab in recurrent/refractory DLBCL: The Spirel study.

5. targetedonc.com targetedonc.com/view/vitalize-trial-explores-maveropepimut-s-pembrolizumab-in-relapsed-refractory-dlbcl

VITALIZE Trial Explores Maveropepimut-S/Pembrolizumab ... We have preliminary data that the use of the immunotherapy maveropepimut-S in the treatment of patients with relapsed diffuse large B-cell ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)59420-0/fulltext

Safety and efficacy results of the combination of DPX ... This study investigates if a synergistic effect leading to enhanced clinical benefits for the subjects can be achieved with the combination of the checkpoint ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10390884/

Maveropepimut-S, a DPX-Based Immune-Educating ... Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03349450

DPX-Survivac and Checkpoint Inhibitor in DLBCL This is a Phase 2 non-randomized, open label, uncontrolled, efficacy and safety study. Study participants will receive two priming doses of 0.5mL of ...

9. targetedonc.com targetedonc.com/view/vitalize-to-validate-the-efficacy-safety-of-maveropepimut-s-plus-pembrolizumab-for-r-r-dlbcl

VITALIZE to Validate the Efficacy/Safety of Maveropepimut- ... A phase 2b study aims to confirm positive efficacy and safety results previously reported with the combination of maveropepimut-S and pembrolizumab