White blood cell.

Details of the initial data from an ongoing investigator-sponsored Phase II clinical trial in which investigators are evaluating DPX-Survivac, a drug being developed by IMV, in combination with low dose cyclophosphamide and Merck?s checkpoint inhibitor pembrolizumab (Keytruda?) in patients with persistent or recurrent/refractory diffuse large B-cell lymphoma (DLBCL), show positive results.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma in the United States and worldwide. The disease accounts for up to one-third of patients with newly diagnosed NHL in the United States.

Photo 1.0: Frederic ?Fred? Ors | Chief Executive Officer of IMV.

DLBCL is also an aggressive form of non-Hodgkin lymphoma that affects B-lymphocytes. Lymphocytes, a type of white blood cell.

Lymphocytes, carries along by the lymph fluid, are part of the immune system and fight infection. B-cells are lymphocytes that make antibodies to fight infections and are an important part of the lymphatic system.

Although DLBCL can occur in childhood, the occurrence is generally increases with age, and most patients are over the age of 60 at diagnosis.

Novel treatment option
DPX-Survivac is new class of immunotherapies that programs targeted T cells in vivo. The drug has demonstrated the potential for targeted, persistent, and durable T cell activation.

According to researchers, the Mode of Action of the drug is key to generating durable solid tumor regressions.

Survivin-based peptide antigens
DPX-Survivac consists of survivin-based peptide antigens formulated using IMV?s proprietary DPX drug development platform. The agent is believed to work by eliciting a cytotoxic T cell immune response against cells presenting survivin peptides.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types. It plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies.

IMV has identified over 15 cancer indications in which the over-expression of survivin can be targeted by DPX-Survivac. As a result, the drug candidate has received Fast Track designation from the United States Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the FDA and the European Medicines Agency (EMA) in the ovarian cancer indication. It is currently being evaluated in multiple Phase Ib/II clinical trials.

Trial results
The preliminary data included assessment of safety and clinical activity (based on modified Cheson criteria) for the first four evaluable patients who have completed their first CT scan after the start of treatment. [1]

The data confirmed that two of the first four evaluable participants showed tumor regressions at the first on-treatment CT scan. The first enrolled participant demonstrated a tumor regression of 48% at first on-treatment scan and the second participant demonstrated a partial response (PR) via a tumor regression of 66% at first on-treatment scan.

Preliminary data from the third participant demonstrated stable disease.

The other participant had early disease progression less than two months following treatment initiation and was discontinued from the study.

The combination therapy appears to demonstrate an acceptable safety profile, with no serious adverse events reported to date.

“These data have provided IMV?s first clinical data for DPX-Survivac in combination with Merck?s Keytruda, and we are encouraged by these early signs of clinical activity in DLBCL,” said Frederic Ors, IMV?s Chief Executive Officer.

“Our clinical results in ovarian cancer have consistently showed that our proprietary T cell technology has the capacity to generate regressions in solid tumors. One of IMV?s key objectives is to provide patients with more effective treatment options by expanding our clinical program to include other hard-to-treat cancer indications. While these data are preliminary, we are pleased to see the promising initial activity in a blood cancer, where checkpoints inhibitors alone have thus far shown modest anti-cancer activity,? Ors added. [2]

Non-randomized trial
Primary Investigator Neil Berinstein, MD, Affiliate Scientist, Sunnybrook Research Institute, Professor of Medicine/Immunology, University of Toronto, is leading the non-randomized, open-label study. The trial is expected to enroll 25 evaluable participants whose DLBCL expresses survivin, a tumor antigen expressed in approximately 60% of DLBCL patients.

Sunnybrook Health Sciences Centre clinicians have, to date, enrolled four patients. Investigators have also started screening and recruiting patients at two additional sites, including at Ottawa Hospital Research Institute and the Research Institute of the McGill University Health Centre.

The study?s primary endpoint is to document the objective response rate. Secondary objectives include measuring tumor regression, and documenting the toxicity profile and durations of response. In addition, researchers will perform analyses to assess circulating antigen specific immune responses and changes in tumor-infiltrating T cell immune responses within the tumor microenvironment. Investigators also plan to assess potential biomarkers of immune and clinical response.

This trial is one of the two Phase II studies evaluating the anti-cancer activity of IMV?s lead candidate, DPX Survivac, in combination with Merck?s pembrolizumab and low dose cyclophosphamide. The other ongoing trial is evaluating the triple combination immunotherapy in patients with advanced ovarian cancer.

Earlier this month IMV confirmed that the company expanded its clinical program with a Phase II basket trial evaluating DPX-Survivac in combination with low dose cyclophosphamide and pembrolizumab in patients with select advanced or recurrent solid tumors.

“The clinical data from our recent ASCO meeting presentation demonstrated for the first time the unique potential of DPX-Survivac to generate solid tumor regressions in ovarian cancer,? Ors said.

“We are delighted to expand our clinical program and collaboration with Merck across multiple cancer indications, and look forward to investigating the potential added benefit of combining DPX-Survivac and pembrolizumab,” he concluded.

[1] Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, et al.Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22.
[2] Study of Nivolumab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) That Have Either Failed or Are Not Eligible for Autologous Stem Cell Transplant (CheckMate 139) – NCT02038933

Last Editorial Review: September 18, 2018

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