Treatment with IMV‘s cancer vaccine DPX-Survivac, combined with intermittent low-dose cyclophosphamide, continues to show promise in women with recurrent, advanced ovarian cancer, updated results from a Phase 1/2 trial show.
Fifteen of the first 19 patients examined for efficacy experienced some level of clinical benefit from the combo treatment, with benefits lasting over six months in seven of them, according to updated data from the DECIDE1 trial (NCT02785250). Treatment was well tolerated, with most side effects being mild to moderate reactions at the injection site.
“We are highly encouraged by the data from DECIDE1, which shows that DPX-Survivac immunotherapy was well tolerated and achieved sustained clinical activity in advanced and recurrent ovarian cancer,” Joanne Schindler, MD, chief medical officer at IMV, said in a press release.
“This is a particularly significant observation in heavily pre-treated patients, for whom remain tremendous unmet need and limited options beyond single-agent chemotherapy, which generates responses in just 12% of patients, with short duration and severe adverse effects,” Schindler said.
DPX-Survivac is a new class of T-cell immunotherapy designed to stimulate the immune system to target and destroy cancer cells, specifically those that have at their surface a protein called survivin.
The therapy consists of small fractions of the survivin protein, which is broadly over-activated in most cancer types and promotes tumor growth. When administered as an under-the-skin injection, DPX-Survivac works as a vaccine, inducing a long-lasting activation of T-cells (immune cells with the ability to fight cancers) against survivin-positive cancers.
The DECIDE1 trial is evaluating a combination of DPX-Survivac and low-dose cyclophosphamide for ovarian cancer patients whose cancer came back after surgery and at least one chemotherapy regimen.
The trial’s main goals are to determine the safety of the combination, the proportion of patients responding to treatment, and the proportion that draws a benefit from the combination. Secondary measures include objective response rate, duration of response, time to progression, and overall survival.
Whether patients develop T-cells specific to the survivin protein, and whether these T-cells are entering the tumors, will also be examined as secondary endpoints.
The last update on DECIDE1’s Phase 2 part showed that all patients with smaller tumors (less than 5 cm at the study’s start) experienced some benefit from the combination treatment, and that infiltration of survivin-specific T-cells into the tumors correlated with tumor regression. At the time, 12 patients had been included in this part, and four had attained a durable partial response.
The company reported updated data after enrolling 22 participants, all of whom are heavily treated, with a median number of three prior therapies. At the time of the analysis, 19 patients had been examined for efficacy, six of whom were still receiving treatment.
Researchers reported that 10 of these patients (53%) had a partial response to treatment, and that an additional five (26%) had disease stabilization, for a disease control rate of 79%.
Clinical benefits lasting over six months were seen in seven (37%) of patients, five of whom were still on treatment. Four of these patients had attained a partial response – deemed as over 30% tumor regression – and three had stable disease, including one with 29.5% tumor regression.
Some of the patients with durable clinical benefits had received prior PARP inhibitors and bevacizumab and failed platinum-based chemotherapy.
While researchers saw a clinical response in patients with different tumor sizes (from 1.5 cm to 7.7 cm), patients with smaller tumors (smaller than 5 cm) had better responses to treatment, with 55% showing clinical benefits lasting six months or more.
“These results demonstrate DPX-Survivac’s clinical potential as a well-tolerated and, possibly, more effective treatment than currently available therapies,” Schindler said. “We believe this outcome places DPX-Survivac at the forefront of a new paradigm in the treatment of ovarian cancer and other solid tumors, as a targeted T-cell therapy that can achieve durable responses while maintaining quality of life.”
“We were pleased to achieve the primary objectives of our DECIDE1 study, showing DPX-Survivac was active, durable and well tolerated in advanced ovarian cancer,” said Frederic Ors, president and CEO of IMV.
IMV plans to present the results to the U.S Food and Drug Administration and discuss the design of a Phase 2b trial to support DPX-Survivac’s accelerated approval.
The FDA granted DPX-Survivac fast track designation as a maintenance therapy in advanced ovarian cancer in 2014. The treatment has also received orphan drug status from the FDA and the European Medicines Agency (EMA) for the same indication.