EO2401 Plus Nivolumab and Bevacizumab Shows Activity in Progressive/Recurrent Glioblastoma

The use of the first-in-class, microbiome-derived therapeutic vaccine EO2401 in combination with nivolumab (Opdivo) with or without bevacizumab (Avastin) produced clinical activity and was well tolerated in patients with progressive/recurrent glioblastoma, according to updated data from the phase 1/2 ROSALIE trial (NCT04116658).¹

In cohort 3 of the study, patients who received EO2401 plus nivolumab and bevacizumab (n = 26) achieved a median overall survival (OS) of 14.5 months. The median duration of response with the triplet was 13.1 months, and the median progression-free survival (PFS) was 5.5 months. The 12- and 18-month OS rates were 57.4% and 43.1%, respectively.

EO2401 plus nivolumab and bevacizumab was also found to be well tolerated. Aside from the incidence of local administration site reactions, the combination’s safety profile was consistent with that of nivolumab and bevacizumab. These findings were presented at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting in Vancouver, British Columbia, Canada.

“Recurrent glioblastoma is one of the most challenging cancers to treat. It is encouraging to see that the robust and durable immune response observed in a significant percentage of patients could translate into promising clinical outcomes in the ROSALIE study. Our hope is now that the improvement in survival associated with the combination regimen of EO2401 with nivolumab and bevacizumab will convert into meaningful therapeutic benefit for patients with brain tumors in large scale studies,” lead investigator and presenting author David Reardon, MD, of Dana-Farber Cancer Institute, stated in a news release.

EO2401 is an off-the-shelf, peptide-based immunotherapy designed to target pre-existing effector memory T cells. These T cells target bacterial peptides, which have cross-reactivity with select tumor-associated antigens, to initiate a rapid cytotoxic response in tumoral cells.

EO2401 is specifically composed of 3 microbial-derived OncoMimics™ peptides that mimic the CD8-positive T-cell epitopes on IL13Ra2, BIRC5, and FOXM1. It also features the helper peptide UCP2, which is a CD4-positive T-cell epitope.²

The multicenter, open-label, first-in-human, ROSALIE trial is being conducted across 10 different clinical sites in Europe and the United States. This study was designed to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2401 in 100 patients, and completed enrollment in December 2022.¹

The study included patients who were at least 18 years of age with unequivocal evidence of first progression/recurrence of glioblastoma according to magnetic resonance imaging, as per RANO criteria. Other key inclusion criteria consisted of at least 1 measurable lesion; human leukocyte antigen (HLA)-A2 positive; an ECOG performance status of 2 or less, or a Karnofsky performance status of 70 or greater; and progression on standard primary therapy, including surgery, radiation, or temozolomide (Temodar), if applicable.³

Patients were excluded from the study if they had received prior treatment with dexamethasone at a dose of 2 mg per day or greater within 14 days of initiating treatment with EO2401, excepting those who required the agent for toxicity management. Other key exclusion criteria included previous treatment with radiotherapy and cytoreductive therapy within 28 days of the first EO2401 administration; prior PD-1– or CTLA-4–directed therapies; and/or systemic anti-tumor treatment or radiotherapy for progressive or first recurrent glioblastoma. Those with significant leptomeningeal disease or extracranial metastases were also not permitted to enroll.

Patients were sequentially assigned to 1 of 3 experimental cohorts, all featuring multiple dose administration of EO2401. In cohort 1, patients are treated with EO2041 alone followed by EO2401 plus nivolumab. In cohort 2, patients received EO2401 in combination with nivolumab. Cohort 3 featured administration of EO2041 plus nivolumab and bevacizumab during the priming phase. Initially, patients who were not located in the United States did not receive bevacizumab as a part of the specified regimens.

The trial protocol was subsequently amended to allow patients outside the United States to receive bevacizumab as a part of the specified regimens, particularly in cohort 3.

The study’s primary end points were safety and tolerability; key secondary end points included OS and immunogenicity of the therapeutic vaccine.

Additional data showed patients experienced rapid and durable immune responses when treated with the combination of EO2401 and nivolumab. Furthermore, CD8-positive T cell responses against EO2401 were observed in 88% of patients in cohort 3, all of whom had CD8-positive T cells that were cross-reactive with the targeted tumor-associated antigens IL13Rα2, BIRC5/survivin, and FOXM1.

In addition to its ongoing investigation in glioblastoma, EO2401 is being evaluated alongside nivolumab in the phase 1/2 SPENCER trial (NCT04187404) in patients with locally advanced or metastatic adrenocortical carcinoma or malignant pheochromocytoma/paraganglioma.²

“We are very pleased to present extensive data from the Phase 1/2 ROSALIE study of EO2401, our lead OncoMimics peptide-based immunotherapy, in glioblastoma,” Pierre Belichard, chief executive officer of Enterome, stated in the news release. “EO2401 continues to generate strong, durable, and target-specific immune responses associated with encouraging efficacy. Based on the promising results presented at SNO 2023, which include an 18-months survival rate of 43%, we now look forward to developing a registrational path for EO2401.”

Editor's Note: Changes to study protocol were made following the original publication of this article. The article has been accordingly updated to reflect major amendments as of March 1st, 2023.

References

1. Enterome’s OncoMimics immunotherapy EO2401 significantly improves survival rate in recurrent glioblastoma. News release. Enterome. November 20, 2023. Accessed November 20, 2023. https://www.enterome.com/news-events/enterome-oncomimics-immunotherapy-eo2401-significantly-improves-survival-recurrent-glioblastoma/
2. Enterome presents positive data from phase 1/2 SPENCER trial of EO2401 in adrenal tumors at ESMO 2023 Congress. News release. Enterome. October 23, 2023. Accessed November 20, 2023. https://www.enterome.com/news-events/enterome-presents-positive-data-from-phase-1-2-spencer-trial-of-eo2401-in-adrenal-tumors-at-esmo-2023-congress/
3. First-in-human, phase 1b/​2a Trial of a multipeptide therapeutic vaccine in patients with progressive glioblastoma (ROSALIE). ClinicalTrials.gov. Updated February 21, 2023. Accessed November 20, 2023. https://clinicaltrials.gov/study/NCT04116658