A novel immunotherapy, EGEN-001, combined with pegylated liposomal doxorubicin (PLD) has demonstrated clinical benefit in recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer patients.
Premal H. Thaker, MD
Premal H. Thaker, MD
A novel immunotherapy, EGEN-001, combined with pegylated liposomal doxorubicin (PLD) has demonstrated clinical benefit in recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer patients, according to a recent NRG/GOG study.
Although the study examined a small population, the results are promising for the potential of immunotherapy agents in ovarian and other similar cancers, according to lead study author Premal H. Thaker, MD, associate professor, obstetrics and gynecology, Division of Gynecologic Oncology, Washington University School of Medicine/Siteman Cancer Center in an interview withTargeted Oncology.
EGEN-001 combines a human IL-12 plasmid that encodes for functional IL-12 with a synthetic DNA delivery system polyethyleneglycol-polyethyleneimine-cholesterol that facilitates plasmid delivery into cancer cells.
Intraperitoneal injection of EGEN-001 is associated with increases in IL-12 levels and its downstream cytokines in the tumor environment without a significant increase in systemic circulation.
The study’s dose escalation model evaluated 3 dose levels of EGEN-001 in 16 evaluable patients. Patients received PLD every 28 days and EGEN-001 on days 1, 8, 15, and 22 of a 28-day cycle. Cycles were repeated every 28 days until disease progression.
A clinical benefit of 57.1% (PR, 21.4%; SD, 35.7%) was found in the 14 patients with measurable disease, with the highest number of partial responses found at dose level three (28.6%). The maximum tolerated dose was not reached.
“We found that we had an almost 86% clinical benefit in our highest dose level, which was level three,” said Thaker. “This was very exciting because, in this patient population, we do not have many treatments available. It was also encouraging, because we did not even have to reach our maximum tolerated dose. We are excited to use this therapy in future studies.”
Efficacy was seen across all three dose levels; however, patients administered dose level three demonstrated the highest level of stabilization of disease. Two patients in the high-level group also had partial responses.
“We found that to be very encouraging because the patient population had been heavily pretreated and do not have many options. The idea of putting together standard chemotherapy and immunotherapy and giving it intraperitoneally, which is a novel administration method for ovarian cancer, is very exciting,” Thaker said.
Side effects included anemia, abdominal pain, and neutropenia. Thaker felt that the toxicity profile was encouraging and hopes to try and push the doses further to determine if better responses may be reached.
Thaker noted that immunotherapy has been studied in ovarian cancer for 20 years, but severe side effects have often occurred in these studies. “With this new agent, we were able to synthesize it differently. Now, we are not seeing those side effects. We are seeing benefit without those harsh side effects. Because of that, we are actually able to combine it with chemotherapy and other agents.”
According to Thaker, determining the maximum tolerated dose will be the next step in the research of this combination. She thinks the novel agent might soon be tested in combination with bevacizumab. “We already know that bevacizumab has a good safety profile in this patient population when paired with chemotherapy, so adding an immunotherapy agent may target a different aspect of the cancer and give us a better result. With these types of novel therapies, we may be able to improve women’s lives.”
Thaker P, Brady W, Bradley W, et al. Phase I study of intraperitoneal IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer administered in combination with pegylated liposomal doxorubicin in recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer patients: an NRG/GOG study.J Clin Oncol. 2015;33 (suppl; abstr 5541).