IMV has completed an amendment to the protocol of its Phase 1/2 clinical trial testing a triple combination of DPX-Survivac, epacadostat, and low-dose chemotherapy in recurrent ovarian cancer. The company now is recruiting participants into its Phase 2 part across multiple sites in the U.S. and Canada.
The announcement follows a meeting with the U.S. Food and Drug Administration in which the design of a future registration trial for accelerated approval also was discussed.
“This FDA meeting was an important milestone for the DPX-Survivac program, and we are very pleased to be aligned with the agency on key aspects of our clinical development plan,” Frederic Ors, chief executive officer at IMV, said in a press release.
DPX-Survivac consists of small fractions of the survivin protein, which is broadly over-activated in most cancer types and promotes tumor growth, according to IMV. Survivin plays an essential role in supporting tumor blood vessel growth and promoting resistance to anti-cancer therapies.
The therapy, administered as an injection under the skin, works by triggering a strong immune response against cancer cells producing the survivin protein, causing them to die.
Epacadostat is a potent, selective oral IDO1 inhibitor. Belonging to the growing class of checkpoint inhibitors, such as CTLA-4, PD-1, and PD-L1 antibodies, IDO pathway inhibitors can regulate immune responses by suppressing tumor cell survival, growth, and invasion.
The Phase 1b/2 trial, called DECIDE1 (NCT02785250), was designed to test a combination of DPX-Survivac, epacadostat and low-dose cyclophosphamide in ovarian cancer patients who received surgery and any number of prior chemotherapies.
The Phase 1b trial included 53 patients who received one of two epacadostat doses — 100 mg or 300 mg — along with the other two therapies. While the treatments were well-tolerated and induced durable responses, responses were better among patients receiving the 100 mg dose of epacadostat.
Based on the findings, IMV and Incyte had agreed to stop dosing patients with epacadostat and continue studying a combination of DPX-Survivac and cyclophosphamide only in the Phase 2 trial.
An additional finding from DECIDE1’s Phase 1b part was that more patients with smaller tumors at baseline — 5 cm or less — responded to the combination (67% had a tumor regression of 30% or more), compared to those with bigger tumors (15%).
The FDA has agreed that the primary endpoint (goal) of the ongoing Phase 2 part is to confirm the benefits of a combination of DPX-Survivac and low-dose cyclophosphamide in patients with smaller tumors.
Besides overall response rate, other measures include the treatment’s safety profile, duration of response, the generation of T-cells against the survivin protein, and T-cell infiltration into tumors.
Depending on Phase 2 results, IMV is planning a follow-up meeting with the FDA to design a pivotal trial with suitable endpoints for the combination’s accelerated approval.
“We believe that, with no currently approved immunotherapy options available, ovarian cancer remains a serious unmet medical need,” said Ors. “We look forward to advancing our ongoing phase 2 DECIDE study in order to potentially expedite DPX-Survivac development as a possible first-in-class T cell immunotherapy treatment for patients with advanced ovarian cancer.”