IMV‘s lead candidate, DPX-Survivac, in combination with Keytruda (pembrolizumab) and low-dose intermittent cyclophosphamide, eliminated radiologic traces of cancer cells in one-third of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients in a Phase 2 trial, the company announced.
The findings from SPiReL (NCT03349450) were shared at the 2019 International Conference on Malignant Lymphoma, June 18–22 in Switzerland. The study, “SPIReL: Phase 2 study DPX-Survivac with intermittent low dose cyclophosphamide and pembrolizumab in patients with recurrent/refractory diffuse large B-cell lymphoma,” was presented by first author Neil Berinstein, MD, FRCPC, ABIM Hematologist at Toronto’s Odette Cancer Centre, Sunnybrook Health Sciences Centre and Affiliate Scientist at Sunnybrook Research Institute.
DPX-Survivac is an investigational immunotherapy designed to activate T cells and boost their ability to recognize and attack cancer cells, specifically those that have at their surface a protein called survivin.
Survivin is a protein that is overproduced in more than 20 solid and blood cancers, including 60% of all DLBCL cases. It plays an important role in the progression of tumors, supporting their survival and growth. It is also associated with more aggressive cancers and their resistance to chemotherapy.
The new therapy is administered as an injection under the skin and is intended to induce a long-lasting activation of cytotoxic T cells against survivin-expressing cancers. This is expected to halt tumor proliferation, elicit tumor cell death, and lead to lasting tumor regression.
The SPiRel Phase 2 trial was designed to evaluate a combination of DPX-Survivac, the immune checkpoint inhibitor Keytruda, and the immunomodulator cyclophosphamide in DLBCL patients who had failed one to three prior lines of therapy. Patients must have failed or been ineligible for an autologous stem cell transplant — a population with few effective treatment options and poor prognosis.
Currently recruiting participants (more information here), the non-randomized, open-label, uncontrolled trial is being conducted at three sites in Canada and is expected to include 25 patients.
Participants will receive two initial doses of under-the-skin DPX‐Survivac 21 days apart, followed by up to six doses every two months. Keytruda will be given as an infusion every three weeks and cyclophosphamide will be taken orally in a seven-days-on/seven-days-off schedule.
SPiRel’s primary goal is to determine the proportion of patients with a reduction in tumor burden over the duration of the study. Secondary measures include tumor regression and duration of response. Researchers will also analyze immune responses from tumor infiltrating T cells in circulation and potential biomarkers of immune and clinical response.
At the time of the analysis, the study had enrolled 11 patients. From the first six patients available for analysis, two achieved a complete response, one achieved a partial response — amounting to an overall response rate of 50% — and two patients had stable disease.
The combination showed a good safety profile, with only two serious treatment-related adverse events reported: low number of white blood cells and low neutrophil levels.
“We are highly encouraged by the level of activity that we are observing with the combination of DPX-Survivac and Keytruda in these patients with DLBCL,” Frederic Ors, IMV’s chief executive officer, said in a press release.
“We believe that the clinical benefits the SPiReL trial has yielded thus far, and the data linking this antitumor activity with the T-cell responses, support DPX-Survivac’s novel mechanism of action and our combination immunotherapy approach. We will continue working with our partners to advance this clinical study toward improving the lives of patients with difficult-to-treat cancers who need better treatment options,” Ors said.