MVP-S Plus Low-Dose Cyclophosphamide Elicits Robust Responses in Recurrent Ovarian Cancer

Oliver Dorigo, MD, PhD

Maveropepimut-S (MVP-S; formerly DPX-Survivac) plus low-dose cyclophosphamide provided clinical benefit to patients with recurrent ovarian cancer, regardless of platinum sensitivity or BRCA mutational status. The durable, survivin-specific T-cell responses observed with the combination further support the continued investigation of peptide cancer vaccine in those with platinum-resistant disease, according to Oliver Dorigo, MD, PhD.

The phase 1b/2, multicenter DeCidE1 trial (NCT02785250) was designed to evaluate MVP-S combined with intermittent low dose of cyclophosphamide in patients with recurrent, epithelial ovarian, fallopian tube, or peritoneal cancer.

Findings, which were presented at the 2023 SGO Annual Meeting on Women’s Cancer, demonstrated that the combination generated an overall response rate of 21% and a disease control rate of 63% in patients with recurrent ovarian cancer. The median time on trial was 4.4 months. However, similar response durability was observed between both platinum-resistant and platinum-sensitive groups. Moreover, translational analyses of biological samples from this study indicate that MVP-S generates substantial T-cell activation.

The regimen was deemed well tolerated, with predominantly grade 1 and 2 toxicities.¹

These results supported the launch of the ongoing phase 2 AVALON study (NCT05243524), which aims to confirm the clinical benefit observed with MVP-S and low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer.²

“This treatment is innovative in many ways,” said Dorigo, who is a member of the Stanford Cancer Institute; an associate professor of obstetrics and gynecologic oncology; and director of the gynecologic oncology fellowship, clinical research group for gynecologic cancer trials, and gynecologic oncology clinical care program at the Mary Lake Polan Gynecologic Oncology Research Laboratory; and director of obstetrics and gynecology in the Division of Gynecologic Oncology at Stanford University Medical Center, Stanford, CA. “…I hope that we can develop a [new] biomarker-driven therapy for patients with recurrent ovarian cancer that uses MVP-S in combination with cyclophosphamide.”

In the interview with OncLive^®, Dorigo explained how MVP-S leverages the DPX platform to produce persistent anti-survivin T-cell and B-cell immune infiltration, highlighted the antitumor activity and safety observed with the combination when given to patients with recurrent ovarian cancer, and described additional research efforts underway.

OncLive^®: Could you describe the unique mechanism of action of MVP-S? How might the agent’s investigation in the DeCidE trial serve to fulfill an unmet need in ovarian cancer?

Dorigo: MVP-S, formerly known as DPX-Survivac, is a water-free, lipid-based formulation that contains five human leukocyte antigen–restricted peptides from a protein called survivin. Survivin is highly expressed in many cancers, including ovarian cancer, and does present a target for immunotherapy. MVP-S is injected under the skin of patients with ovarian cancer. It is taken up by antigen-presenting cells that subsequently stimulate T cells and B cells in local lymph nodes. The survivin-specific T cells and survivin antibodies produced by B cells, systemically circulating, detect the survivin expression on tumor cells and have cytolytic activity.

We did this research because patients with recurrent ovarian cancer, particularly those who are not candidates for platinum-based chemotherapy due to the development of resistance mechanisms, need more effective treatments that are better tolerated.

What was the design of this study?

The DeCidE trial enrolled 22 patients with recurrent ovarian cancer. [About] 60% of these patients were platinum resistant and [about] 40% were platinum sensitive. The patients were treated with a subcutaneous injection of MVP-S [given] twice in 3-week intervals, followed by MVP-S injection every 8 weeks for up to a year. For some patients [MVP-S was given] beyond that. MVP-S treatment was combined with cyclophosphamide, which was given [at a dose of] 50 mg twice a day, on a 1-week-off/1-week-on schedule.

What efficacy findings from the study were presented at the 2023 SGO Annual Meeting?

Data from the DeCidE trial show clinical efficacy in 21% of patients who had partial responses to the treatment. Out of the 11 patients with platinum-resistant disease, 4 [continued] treatment beyond 6 months, showing that this could be a durable treatment. [Additionally], 4 out of 8 patients with platinum-sensitive disease were treated beyond 1 year. We further showed that patients whose tumors have an increased number of immune effector cells prior to treatment, particularly T cells and B cells, tend to have a better response to treatment. We also demonstrated that MVP-S treatment induces very strong anti-survivin T-cell responses in about 87% of patients.

We have mapped the tumor environment extensively, and some of our current data show that the Wnt/β-catenin pathway is highly upregulated in patients who do not [experience] a response to treatment. We could potentially study this biomarker [further] as a response predictor or [for] the development of a biomarker-driven approach using MVP-S and cyclophosphamide.

What was learned in terms of safety?

[The combination of] MVP-S and cyclophosphamide is well tolerated. We have seen some local reactions at the injection site of MVP-S. The systemic [AEs include] fatigue and some nausea, but those are commonly observed symptoms in [patients with] ovarian cancer. Since this is a single-arm study, we don’t know whether [those toxicities are] truly related to the product.

These findings have supported the continued investigation of MVP-S and cyclophosphamide in the phase 2 AVALON trial. Please provide a quick overview of the design, eligibility criteria, and key objectives of this trial.

The AVALON trial [takes] our current observation and further expands [exploration of the combination] into a larger cohort of patients with platinum-resistant disease. We currently plan to enroll at least 73 patients who had not [received] more than 4 prior lines of chemotherapy. Patients cannot have had immune checkpoint inhibitors [ICIs], and their lesions cannot be greater than 4 cm. Those are the basic inclusion criteria. One of the goals of the study is to obtain tumor biopsies prior to treatment, and [perform] a very careful analysis of molecular predictors of response to MVP-S.

What is your take-home message to your colleagues regarding this research?

MVP-S has shown some very positive signals in our first cohort of patients, [although] we don’t have a sufficiently high number of patients to be conclusive about the response rates. I’m looking forward to [seeing] the response rates in the AVALON trial, and I’m particularly excited about the research we’re currently conducting on tumor biopsies in patients undergoing this treatment.

What other data presented at the meeting did you find to be particularly exciting?

It’s [been] another exciting SGO Annual Meeting. We were all excited to see the [research] that combines ICIs with chemotherapy in patients with metastatic endometrial cancer. We do know that these studies read out as positive, but we are waiting for the magnitude of their effect. [These findings] could potentially change the way we think about the treatment of patients with metastatic endometrial cancer and change a paradigm.

Editor’s Note: Dr Dorigo reports serving as an independent contractor or in an advisory role for IMV, GSK, Genentech, Merck, and Epsila Bio. He received grants or research funding from IMV, AstraZeneca, Bioeclipse, Genentech, Millenium, Novartis, and Pharmamar.

References

1. Dorigo O, Oza A, Pejovic T, et al. Maveropepimut-S, an immune-educating therapy with durable clinical benefit in patients with recurrent ovarian cancer. Presented at: 2023 Annual Meeting on Women’s Cancer; March 25-28; Tampa, Florida. Poster 180.
2. Maveropepimut-S (MVP-S) and low-dose CPA in patients with platinum-resistant ovarian cancer (AVALON).Clinicaltrials.gov. Updated December 23, 2022. Accessed March 30, 2023. https://clinicaltrials.gov/ct2/show/NCT05243524