DPX-Survivac Reaches Safety, Response End Points in Advanced Ovarian Cancer

Updated results from the phase II arm of the DeCidE1 trial of DPX-Survivac demonstrated promising activity and tolerability in patients with heavily pretreated, advanced recurrent ovarian cancer, according to the developer of the agent IMV Inc.

“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.” Frederic Ors, president and chief executive officer at IMV stated in a press release.

Out of 19 patients who were evaluable for efficacy, 15 (79%) achieved disease control with either stable disease or a partial response in the target lesions. Ten patients (53%) demonstrated tumor shrinkage.

“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,” said Joanne Schindler, MD, DVM, chief medical officer at IMV.

“This is a particularly significant observation in heavily pretreated patients, for whom there remains a tremendous unmet need with limited options beyond single-agent chemotherapy, which generates responses in just 12% of patients with short duration and severe adverse effects.”

Clinical benefit lasting ≥6 months was observed in 7 patients, 4 (21%) of whom achieved a partial response with >30% tumor regression on target lesions. Three patients had ongoing stable disease for more than 6 months (range, 7-9).

Durable clinical benefit was seen during an analysis of baseline tumor burden (BTB), with more patients in this arm of the study having BTB <5 cm compared with any other arm of the study. Six out of 11 patients achieving this BTB <5 cm demonstrated clinical benefit for more than 6 months.

Treatment was well tolerated, with most toxicity events being grade 1/2 in severity at the injection site.

&ldquo;These results demonstrate DPX-Survivac&rsquo;s clinical potential as a well-tolerated and, possibly, more effective treatment than currently available therapies,&rdquo; Schindler said. &ldquo;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.&rdquo;

Patients who benefitted from this agent included those with platinum-resistant and refractory disease. Patients included in this analysis had a median number of prior lines of therapy greater than 3.

The trial under evaluation is a phase Ib/II study evaluating the T-cell activating therapy DPX-Survivac with low-dose, oral cyclophosphamide and the IDO1 inhibitor epacadostat in patients with recurrent ovarian, fallopian tube, or peritoneal cancer with safety and efficacy end points. The primary end point of the phase II portion is objective response rate. Other outcome measures include duration of response, cell-mediated immunity as measured by antigen-specific response in peripheral blood, time to progression, and overall survival.

For inclusion in the study, patients had to have histologically confirmed, stage IIc to IV disease; evidence of progressive disease; measurable disease by RECIST 1.1; an ECOG performance status of &le;1; and a life expectancy that is more than 6 months. Both platinum-resistant and -sensitive patients could be included, with multiple prior lines of chemotherapy allowed.

Patients who were eligible for curative treatments and those who received prior survivin-based vaccines, immune checkpoint inhibitors, or IDO inhibitors were ineligible to receive therapy on the trial.

DPX-Survivac consists of 5 unique human leukocyte antigen—restricted survivin peptides formulated in IMV&rsquo;s drug delivery platform. It has activity against survivin-expressing cancer cells by inducing cytotoxic CD8-positive T-cell responses.

DPX-Survivac had previously received Fast Track designation from the FDA as maintenance therapy in patients with advanced ovarian cancer. IMV plans to use these results during a type B meeting with the agency to discuss the design of a phase IIb trial.

Reference:

IMV Inc. announces breakthrough data from DeCidE1, its ongoing phase 2 study of DPX-Survivac in patients with advanced recurrent ovarian cancer. IMV Inc: February 25, 2020. bit.ly/2T0tGj9. Accessed February 26, 2020.