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December 3, 2020 — The survivin-targeted T-cell therapy DPX-Survivac, when used in combination with intermittent low-dose cyclophosphamide, prolonged clinical benefit with promising tolerability in patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer.
The survivin-targeted T-cell therapy DPX-Survivac, when used in combination with intermittent low-dose cyclophosphamide (CPA), prolonged clinical benefit with promising tolerability in patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer, according to updated clinical and translational data from the phase 2 DeCidE1 trial (NCT02785250).1
Results showed 78.9% (n = 15) of 19 patients experienced clinical benefit from the treatment in the form of partial responses or stable disease. Thirty-seven percent (n = 7) of patients achieved durable clinical benefit over 6 months. Moreover, 26.3% (n = 5) experienced clinical benefit for about 1 year (range, 11 months-16 months), with 2 patients still achieving benefit.
The median progression-free survival (PFS) with the approach was 4.47 months, and PFS rates at 6 months and 12 months were 39% and 20%, respectively. These data were found to be consistent with other immunotherapies in other cancer indications, according to IMV Inc, the developer of the therapy. Additionally, the overall survival (OS) rate with the treatment at 12 months was 66.1%. More than half of participants are still alive, and the median OS has not yet been reached.
“These results…clearly support the relevance of DPX-Survivac as a potential new and much-needed treatment option for advanced recurrent ovarian cancer, a hard-to-treat indication where other immunotherapies have thus far had limited success and where there is a high unmet medical need for patients who have failed chemotherapy and PARP inhibitors,” Fred Ors, president and chief executive officer of IMV, stated in a press release.
DPX-Survivac represents a new class of targeted immunotherapies. The product was developed to induce antigen-specific, functional, robust, and continued de novo T cell response, according to IMV, Inc. The mechanism of action of the therapy is hypothesized to elicit durable tumor regressions.
In December 2014, the product received a fast track designation from the FDA and in July 2015 as maintenance therapy in patients with advanced ovarian cancer, DPX-Survivac received an orphan drug designation; it also has orphan drug designation status in ovarian cancer from the European Medicines Agency.
In the multicenter, open-label, phase 2 trial, investigators set out to examine the safety and efficacy of DPX-Survivac plus intermittent low-dose CPA for increasing the level of survivin-specific T cells in patients with recurrent, advanced platinum-sensitive and -resistant ovarian cancer. Nineteen evaluable patients were enrolled to the trial and all had advanced disease with the exception of 1 patient. Moreover, 12 patients had received 3 or more previous lines of treatment.
In the trial, participants were given 2 subcutaneous injections of DPX-Survivac 3 weeks apart and then every 8 weeks afterward in combination with intermittent low-dose CPA 1-week-on and 1-week-off for up to 1 year.
The primary end points of the trial comprised overall response rate, disease control rate, and safety. Key secondary end points comprised cell-mediated immunity, immune cell infiltration in biopsy samples, duration of response, time to disease progression, overall survival, and biomarker assessments.
Additional results from extensive translational analyses that are still ongoing have revealed a link between the survivin-specific T cells and clinical benefit, thus supporting the mechanism of action of the treatment.
Specifically, examination of peripheral blood mononuclear cells (PBMC) samples collected from 16 evaluable patients showed that 87% (n = 14/16) had a survivin-specific CD8+ T cell response associated with the treatment. Moreover, therapy-induced infiltration of survivin-specific T cell clones into the tumors was observed as early as day 56 after treatment initiation.
The treatment was also found to be well tolerated, with most of the associated toxicities being grade 1 in severity; the majority of these adverse effects were injection site reactions.
“With these results, DPX-Survivac continues to exhibit significant and durable antitumor activity, paving the way for targeted T-cell therapies in advanced recurrent ovarian cancer and other solid tumors,” Joanne Schindler, MD, DVM, chief medical officer at IMV, added in the release. “DPX-Survivac also continues to be well-tolerated, which is especially meaningful compared to single-agent chemotherapy and other approaches in development.”
Earlier results from the trial showed that 79% (n = 15) of patients achieved disease control with the treatment and 53% (n = 10) experienced a reduction in their tumors.2 Seven patients experienced benefit that persisted for 6 months or longer. Notably, 21% (n = 4) of these patients had a PR and tumor regression of over 30% on target lesions. Three patients achieved stable disease for longer than 6 months.
Additionally, an analysis of baseline tumor burden (BTB) revealed that the treatment resulted in durable clinical benefit in this patient population. More participants in this arm had BTB that was less than 5 versus any other arm examined in the trial. Of 11 patients assessed, 6 of those who achieved BTB of less than 5 cm had clinical benefit that persisted for over 6 months.