Dr Dorigo on the Clinical Benefit with Maveropepimut-S in Recurrent Ovarian Cancer

Oliver Dorigo, MD, PhD, member, Stanford Cancer Institute; associate professor, obstetrics and gynecologic oncology, Stanford University Medical Center; director, gynecologic oncology fellowship, clinical research group for gynecologic cancer trials, gynecologic oncology clinical care program, Mary Lake Polan Gynecologic Oncology Research Laboratory, and obstetrics and gynecology, Division of Gynecologic Oncology, Stanford Health Care, discusses the clinical efficacy of maveropepimut-S (MVP-S) in patients with recurrent ovarian cancer.

The use of MVP-S plus an intermittent low dose of cyclophosphamide in patients with advanced recurrent ovarian cancer was evaluated in the phase 1b/2, multicenter DeCidE1 trial (NCT02785250), Dorigo begins. The trial enrolled patients with recurrent, epithelial ovarian, fallopian tube, or peritoneal cancer. Patients were randomized to MVP-S and cyclophosphamide with or without the recommended phase 2 dose of epacadostat. Primary end points included overall response rate (ORR), disease control rate (DCR), and safety. 

In the study, MVP-S and cyclophosphamide demonstrated clinical benefit in this population, with an ORR of 21% and DCR of 63%, Dorigo states. Of the 11 patients with platinum-resistant disease, 4 were treated beyond 6 months, Dorigo says. Similarly, 4 out of 8 patients with platinum-sensitive disease were treated beyond 1 year, he adds. These data indicate that the combination can elicit durable responses in patients regardless of platinum sensitivity, Dorigo explains.

Patients with an increased number of immune effector T cells and B cells were found to experience a heightened response to treatment, Dorigo continues. Furthermore, MVP-S plus cyclophosphamide produced a positive survivin-specific T-cell response in 87% of patients, he notes.

Investigation of the tumor microenvironment revealed that genes involved in the WNT/beta-catenin signaling pathway are highly upregulated in patients who do not respond to this regimen, indicating their potential predictive value, Dorigo details. Future research may evaluate the utility of these genes in designing biomarker-driven approaches in ovarian cancer, he concludes.

Dr Dorigo reports serving as an independent contractor or in an advisory role for IMV, GSK, Genentech, Merck,

Epsila Bio; he received grants or research funding from IMV,

AstraZeneca, Bioeclipse, Genentech, Millenium, Novartis,

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Oliver Dorigo, MD, PhD, discusses the clinical efficacy of maveropepimut-S in patients with recurrent ovarian cancer.

 Dr Dorigo on the Clinical Benefit with Maveropepimut-S in Recurrent Ovarian Cancer

Oliver Dorigo, MD, PhD, associate professor of Obstetrics and Gynecology, Stanford University Medical Center, Stanford Medicine, discusses the use of immunotherapy in the treatment of patients with ovarian cancer.

Early trials have shown that tumor infiltrating lymphocytes that are extracted from a patient's tumor, expanded in cell culture in the laboratory, and then reinfused into the patient can induce significant antitumor activity, explains Dorigo. However, responses with single-agent immune checkpoint inhibitors have been modest, ranging from 10% to 15%. Though patients are benefitting from these agents, researchers are modifying the therapy so that T cells are better able to target the cancer cells.

Another strategy is combination approaches, says Dorigo. Promising early efficacy has been shown by combining immune checkpoint inhibitors with PARP inhibitors. Though PARP seems to show the biggest impact in patients with 

 mutations, responses have also been observed in patients without 

Oliver Dorigo, MD, PhD

Articles

Dr Dorigo on the Clinical Benefit with Maveropepimut-S in Recurrent Ovarian Cancer

Dr. Dorigo on Immunotherapy in Ovarian Cancer