The subcutaneously administered peptide cancer vaccine maveropepimut-S was found to produce promising activity in heavily pretreated patients with recurrent ovarian cancer.
The subcutaneously administered peptide cancer vaccine maveropepimut-S (formerly DPX-Survivac) was found to produce promising activity in heavily pretreated patients with recurrent ovarian cancer, according to final topline data from the phase 1/2 DeCidE1 trial (NCT02785250).1
At 23.8 months of follow-up, treatment with the vaccine resulted in an overall survival (OS) rate of 44.9%, with a median OS was 19.9 months in this patient population. The approach was also reported to have favorable tolerability.
“The overall results obtained from the DeCidE1 trial are very promising,” Oliver Dorigo, MD, PhD, principal investigator of the study and director of the Gynecologic Oncology Service at Stanford University, stated in a press release. “…These results are particularly encouraging because many subjects in the trail had been heavily pretreated and 57.9% were platinum resistant. We believe that these results support the further clinical study of maveropepimut-S in ovarian cancer.”
Data from an extensive analysis of collected biological samples, which represented key secondary end points of the trial, showed that the vaccine was able to prompt the generation of tumor antigen–specific T cells.
“Importantly, these analyses affirm the molecular and cellular mechanism of maveropepimut-S based therapy,” Jeremy Graff, MD, chief scientific officer of IMV Inc., stated in a press release. “These data will also inform the discussion and design of a phase 2 clinical study to be submitted to the FDA.”
Detailed data from the translational analyses have been submitted for presentation at an upcoming medical meeting, according to IMV Inc.
Maveropepimut-S was designed to generate cancer-targeted T cells in vivo by combining the DPX platform and the cancer antigen survivin.2 When the vaccine is administered via a subcutaneous injection, antigen-presenting cells recruit to the injection site and take up survivin to present to naïve T cells.
From there, the cells migrate to the lymph nodes and present survivin to naïve T cells through the MHCII and the T-cell receptor. This process activates trafficking of activated cytotoxic T cells (CTLs) into the blood. The CTLs then infiltrate the tumor, recognize the survivin on the surface of the cancer cells, and release cytotoxic molecules that can kill the tumor.
Previously, the vaccine has showcased a robust and sustained antigen-specific immune response with the infiltration of the T cells into the tumor following treatment; this has been linked with durable clinical activity that can persist for 2 years or longer.
In the multicenter, randomized, open-label DeCidE1 trial, investigators set out to examine the safety and effectiveness of maveropepimut-S in combination with intermittent low-dose cyclophosphamide (CPA).
A total of 22 patients with recurrent, advanced, platinum-sensitive and -resistant ovarian cancer. To be eligible for enrollment, patients needed to have histologically confirmed, stage IIC to IV epithelial ovarian, fallopian tube, or peritoneal cancer, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a life expectancy of at least 6 months.3
Patients who were candidates for otherwise curative treatment or who were undergoing concurrent therapy were excluded from the trial. Other exclusion criteria included previous treatment with survivin-based vaccines or immune checkpoint inhibitors, a concurrent second malignancy beyond non-melanoma skin cancer, clinical ascites, a single lesion at least 4 cm, a malignant bowel obstruction, and a history of autoimmune disease that required treatment within the past 2 years, among others.
Participants were administered 2 subcutaneous injections of the vaccine 3 weeks apart and every 8 weeks thereafter, in addition to intermittent low-dose CPA 1-week-on and 1-week-off until the end of treatment. Biopsies of tumor tissue were done before and while on treatment.
The primary end points of the trial included overall response rate, disease control rate, and safety. Key secondary end points comprised cell-mediated immunity, immune cell infiltration in paired biopsy samples, duration of response, time to progression, OS, and biomarker analyses.
“The protein survivin is found in more than 15 types of solid tumor and hematologic cancers. It has been recognized as a promising tumor-associated target because it is overexpressed in a high percentage of tumor types,” according to IMV, Inc. “Survivin plays a critical role in tumor biology…we believe maveropepimut-S’ ability to deliver a sustained flow of T cells that target surviving expressed on cancer cells can lead to more clinically effective antitumor therapies.”