Positive Preliminary Phase 2 Data Reported for DLBCL Combination Therapy

IMV Inc. recently announced positive preliminary data collected from its phase 2 clinical trial evaluating a combination therapy consisting of anti-cancer immunotherapy, DPX-Survivac, in combination with low dose cyclophosphamide and Merck’s pembrolizumab (Keytruda) for the treatment of diffuse large B-cell lymphoma (DLBCL). The therapy was found to have an acceptable safety profile, with patients showing tumor regression and/or stable disease.

“This type of lymphoma remains a significant unmet medical need in today’s treatment landscape,” Frederic Ors, BSc, MSc, chief executive officer of IMV Inc., told Rare Disease Report^®. “There is a poor prognosis for DLBCL patients who are not cured by first-line chemotherapy, and there is an increasing incidence of the disease in elderly patients who often cannot tolerate the current standard-of-care.”

Investigators anticipate enrolling 25 participants whose DLBCL expresses survivin—a tumor antigen expressed in more than half of patients with the cancer—in the phase 2, interventional, open-label, single group assignment trial. Data pertaining to the first 4 evaluable participants were included in the announcement.

“DLBCL has an overexpression of the survivin protein—in approximately 60% of patients, I believe,” Ors explained. “DPX-Survivac’s mechanism of action targets survivin and elicits 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 many cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies.”

The primary goal of the trial is to document the objective response rate, while secondary objectives include measuring tumor regression (timeframe of 1 year) and documenting the combination therapy’s toxicity profile (1 year) and duration of responses (2 years).

Participants will receive 2 priming doses of DPX-Survivac (0.5 mL) 21 days apart and up to 6 booster vaccinations (0.1 mL) bi-monthly with low dose metronomic oral cyclophosphamide (50 mg twice a day) for the duration of 1 year or until disease progression—whichever occurs first.

Half of the 4 participants included in the preliminary data demonstrated tumor regressions at the first on-treatment CT scan; the first participant showed a tumor regression of 48% at first on-treatment scan, and the second showed a partial response to the treatment via a tumor regression of 66% at first on-treatment scan. The third participant was observed to have stable disease. The fourth participant was discontinued from the trial as he/she demonstrated early disease progression less than 2 months after treatment was initiated.

Overall, an acceptable safety profile was observed as no serious adverse events were reported.

“These are our first clinical data assessing the safety and efficacy of the DPX-Survivac/pembrolizumab combination,” Ors emphasized to RareDR ^®. “While they are preliminary, we are encouraged by the potential signals of clinical benefit, with 3 out of 4 first patients treated showing responses at first CT scan and tumor reductions (-66% and -48%) in 2 of them. In addition, thus far, the combination appears to have a tolerable safety profile, with no serious adverse events reported.”

Looking forward, investigators on the trial also plan to analyze circulating antigen-specific immune responses and changes in tumor-infiltrating T cell immune responses within the tumor microenvironment in addition to evaluating potential biomarkers of immune and clinical response.

“Investigators are in the process of completing enrollment of 25 patients,” Ors said. “We hope to have topline data from all evaluable patients in the first half of 2019.”

This trial is just 1 of the 2 phase 2 trials evaluating the effectiveness of DPX Survivac in combination with Merck’s pembrolizumab and low dose cyclophosphamide. The other trial is evaluating the treatment in patients with advanced ovarian cancer.