Phase 2 DeCidE1 Trial Reports Final Topline Results on the Efficacy of Maverpopepimut-S in Advanced Recurrent Ovarian Cancer

Maveropepimut-S (Previously DPX-Survivac) demonstrated promising results in a population of patients with advanced recurrent ovarian cancer in the phase 2 DeCidE1 trial (NCT02785250), according to a press release from IMV Inc.1

Final topline findings from the trial indicated that the median overall survival (OS) was 19.9 months with an OS rate of 44.9% at 23.8 months. Results from the study are particularly promising, as numerous patients were pretreated and over half (57.9%) were platinum resistant, according to principal investigators Oliver Dorigo, director of the gynecologic oncology service at Stanford University. These data come after the final patients completed the study following over 2 years of clinical benefits with maveropepimut-S.

The secondary end point of this study includes an extensive analysis of collected biological samples. Additional results and the translational analysis have been submitted to an upcoming scientific meeting.

“The translational analyses provide strong evidence that maveropepimut-S successfully elicits the generation of tumor antigen-specific T cells. Importantly, these analyses affirm the molecular and cellular mechanism of [ maveropepimut-S] based therapy. [These] data will also inform the discussion and design of a phase 2 clinical study to be submitted to the FDA,” Jeremy Graff, MD, chief scientific officer of IMV, said in a press release.

The phase 1b/2 multicenter, randomized, open-label trial enrolled 22 patients for the phase 2 portion with recurrent, advanced platinum-sensitive and resistant ovarian cancer. Patients received 2 subcutaneous injections of maveropepimut-S 3 weeks apart and every 8 weeks thereafter, with an intermittent low-dose of cyclophosphamide 1 week on and 1 week off until the end of treatment. Additionally, tumor biopsies were taken before and during treatment.

During phase 1b of this study, the goal was to evaluate the safety and effectiveness of maveropepimut-S and determine the recommended phase 2 dose of epacadostat (INCB024360) in combination with maveropepimut-S and cyclophosphamide.

The primary end points of the study were overall response rate, disease control rate, and safety, with secondary end points including cell mediated immunity, immune cell infiltration, in paired biopsy samples, duration of response, time to progression, OS, and biomarker analysis.

Patients were required to have histologically confirmed stage IIc to IV epithelial ovarian, fallopian tube or peritoneal cancer, platinum-resistant or -sensitive and have completed their first-line treatment with evidence of disease progression.

In a previous trial, maveropepimut-S induced robust T-cell responses in a population of patients with advanced ovarian cancer (n = 121).2 A total of 121 patients with platinum-sensitive or -resistant ovarian, fallopian tube or peritoneal cancer were enrolled who were treated with maveropepimut-S with or without drug combinations. Investigators pulled data from 3 clinical trials (NCT01416038; NCT03332576; NCT02785250) in order to assess immune responses, tumor immune infiltrates, and clinical tumor responses. Patients were enrolled in both maintenance (n = 56) and recurrent (n = 65) disease settings.

Findings from the study indicated that maveropepimut-S–generated survivin-specific T cells were identified in 80% of patients. Survivin-specific T cells were also found in the tumor microenvironment post-treatment using TCR-β sequencing. Anti-tumor responses correlated with an increase in T cells following treatment of maveropepimut-S. Additionally, an increase in T-cell signaling was identified in post-treatment tumor tissue through RNA sequencing along with upregulation of cytotoxic markers, natural killer cells and B cell. These studies showed that the T cells retained their functionality throughout treatment. Investigators concluded that maveropepimut-S stimulated a notable anti-tumor response through robst and durable survivin-specific T cell responses and increasing infiltration of target-specific T cells into tumors.

References:

1. IMV announces final topline results of the DeCidE1 clinical trial in advanced recurrent ovarian cancer. News Release. August 10, 2021. Accessed August 20, 2021. https://bit.ly/3AYP4c0

2. Dorigo O, Fiset S, MacDonald L, et al. DPX-Survivac, a novel T-cell immunotherapy, to induce robust T-cell responses in advanced ovarian cancer. J Clin Oncol. Published Online February 4, 2021;38(5):suppl 6. doi: 10.1200/JCO.2020.38.5_suppl.6