A microbiome-derived therapeutic vaccine (EO2401) has demonstrated immune responses and anticancer activity in combination with nivolumab and bevacizumab in patients with recurrent glioblastoma, one of the most difficult-to-treat cancers, according to data presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting.¹ The results of the phase I/II EOGBM1-18/ROSALIE study showed improved progression-free and overall survival with the triplet combination therapy. With follow-up of more than 14 months, median survival has still not been reached. The combination was also well tolerated, with no unexpected side effects, study authors reported.

“We saw robust immune responses, and some of them were quite early,” said lead study author David A. Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School, Boston. “The addition of bevacizumab to this population of very challenging patients allowed them to stay on the study longer, and we think improve their efficacy. The combination of bevacizumab plus EO2401 and nivolumab seems to have the strongest efficacy signal, and we have amended the study to include additional patients in this cohort,” Dr. Reardon added.

David A. Reardon, MD

The EO2401 vaccine is composed of three high-affinity, microbial-derived synthetically produced peptides that mimic CD8-positive T-cell HLA-A2 epitopes from the tumor-associated antigens IL-13Rα2, BIRC5/survivin, and FOXM1, and the helper CD4-positive peptide UCP2. EO2401 is administered subcutaneously with the adjuvant Montanide (a mixture of oil and water combined with a specific antigen to boost the immune response to that antigen).

Study Methods

Patients enrolled in the ROSALIE study had glioblastoma at first disease progression or recurrence following standard care surgery, concurrent radiation therapy and temozolomide, and adjuvant temozolomide. All patients received the anti–PD-1 inhibitor nivolu­mab, and some also received the VEGF inhibitor bevacizumab. 

The ROSALIE study initially began with three cohorts of patients who received a combination of EO2401 plus nivolumab. Early into the study, however, investigators amended the schema to allow low-dose bevacizumab, which is approved by the U.S. Food and Drug Administration for recurrent glioblastoma in the United States, in addition to EO2401 and nivolumab.

“Bevacizumab decreases cerebral edema, can improve neurologic deficits, and may allow patients with this recurrent, aggressive disease to stabilize clinically and stay on study potentially long enough to receive a therapeutic benefit,” explained Dr. Reardon.

Key Findings

The only side effects associated with EO2401 were localized reactions, which were low-grade and manageable in most patients. The data also showed the “typical spectrum of immune-related adverse events associated with nivolumab,” said Dr. Reardon. 

In terms of immune responses, analysis showed fast, strong, and durable CD8-positive T-cell response, with strong cross-reactivity against tumor-associated antigens, he continued. “We saw immune responses detectable as early as 2 weeks after initiation of vaccination,” said Dr. Reardon, who noted the responses were maintained and durable. 

Dr. Reardon and colleagues also analyzed the correlation between systemic immune response and outcome. According to preliminary data, patients who had systemic immune responses seemed to have a greater likelihood of progression-free survival.

Patients who received bevacizumab in combination with EO2401 and nivolumab had the best progression-free and overall survival rates, said Dr. Reardon. Whereas those who received EO2401 and nivolumab “declined very rapidly” and came off study “too early to allow therapeutic benefits.” For patients who received the triplet combination, median survival has still not been reached, with a follow up of 14.1 months. “The durability of the responses in this study is very encouraging,” said Dr. Reardon. 

DISCLOSURE: Dr. Reardon reported financial relationships with Advantagene, Agenus, Agios, Anheart Therapeutics, Bayer, Bristol Myers Squibb, Delmar Pharmaceuticals, Ellipses Pharma, EMD Serono, Genenta Science, lmvax, Kintara Therapeutics, Kiyatec, Medicenna, Merck, Merck KGdA, Novocure, Oncorus, Regeneron, Taiho Pharmaceutical, and Vivacitas Oncology.

REFERENCE

1. Reardon D, et al: 2022 SITC Annual Meeting. Abstract 642. Presented November 10, 2022.