DPX-Survivac + Pembrolizumab for Lymphoma

(VITALIZE Trial)

Recruiting at 43 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

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?

Pembrolizumab has shown significant clinical efficacy in Hodgkin Lymphoma and some subtypes of non-Hodgkin Lymphoma, which share genetic features with Hodgkin Lymphoma, have shown promising responses in early phase trials. ^{1 2 3 4 5}

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. ^{1 2 6 7 8}

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. ^{2 3 5 9 10}

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.

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

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
• 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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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, 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]

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 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]

References

1. England 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. [2020]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. United States 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. [2021]

8. England 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. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. [2022]