VXM01 Vaccine/Avelumab Displays Safety, Early Clinical Activity in GBM

Exploratory biomarker investigations indicated possible pharmacodynamic and predictive biomarkers for tumor response associated with VXM01.

VXM01, an investigational, oral, anti-VEGFR vaccine, was found safe and showed early signs of efficacy with avelumab (Bavencio) for recurrent glioblastoma (GBM) in final findings from phase 2a VXM01-AVE-04-INT trial (NCT03750071).¹

The combination was shown to be well tolerated, and most adverse effects (AEs) were mild or moderate in severity, according to a news release. No serious AEs were attributed to VXM01, and 81.8% of serious AEs were attributed to recurrent GBM. These safety and tolerability findings were consistent with previously reported data with avelumab monotherapy. No new safety signals were observed with the combination.

“The completion of this phase 2a study is a significant milestone for Vaximm AG, as it provides strong evidence that VXM01, in combination with avelumab, is generally well tolerated in patients with recurrent GBM,” Constance Hoefer, PhD, chief executive officer of Vaximm AG, stated in the news release. “We are encouraged by these early results and the potential to improve outcomes for patients with this aggressive cancer. We remain committed to advancing VXM01 as a key therapeutic candidate for the treatment of glioblastoma, other cancers, and other diseases where VXM01 may have positive impact on treatment outcomes.”

Among patients with unresected disease, the overall response rate (ORR) with the combination was 12.0%; all responses were partial, and an additional 4.0% of patients had stable disease. Among patients with resected disease, the median overall survival (OS) ranged from 2.2 months to 46.5 months. In the overall evaluable population (n = 25), the median time to progression (TTP) was 2.7 months (95% CI, 2.7-2.7; range, 0.3-22.1), and the median OS was 11.1 months (95% CI, 8.5-16.3; range, 3.8-38.2). Additionally, responders experienced decreases in tumor size, regardless of baseline tumor size, showing the potential efficacy of VXM01 for patients with large tumors, as well as those with small tumors or early-stage disease, according to the news release.

Notably, exploratory biomarker investigations identified potential pharmacodynamic and predictive biomarkers for VXM01-associated tumor response.

VXM01 is an oral T-cell immunotherapy that activates T cells to attack tumor vasculature and/or cancer cells, depending on the tumor type. This agent stimulates the immune system to activate VEGFR2-specific cytotoxic T cells that then destroy tumor vasculature cells, facilitating increases in immune cell infiltration into the tumor. VEGFR2 is highly overexpressed on cancer cells in multiple tumor types, including brain cancer. In the preclinical setting, a murine analog VXM01 vaccine had broad antitumor activity—including VEGFR2-specific T-cell response—across tumor types, and was shown to destroy tumor vasculature and increase immune cell infiltration.

The VXM01-AVE-04-INT trial enrolled patients at least 18 years of age with histologically diagnosed intracranial supratentorial malignant glioma (glioblastoma per World Health Organization grade IV criteria) who had evidence of tumor progression by Response Assessment in Neuro-Oncology criteria after 1 or more prior lines of therapy that must have contained radiation (completed 3 or more months prior to enrollment) and chemotherapy with temozolomide; adequate bone marrow, hepatic, and renal function; no active bacterial infection requiring antibiotic treatment; and a Karnofsky performance status of at least 70.² Patients in the resectable arm also needed to be candidates for a tumor reoperation.

The primary outcome was safety and tolerability. Secondary outcomes included TTP, progression-free survival, recurrence-free survival, OS, ORR, and duration of response.

Notably, a prior phase 1 randomized, double-blind, placebo-controlled trial of VXM01 was conducted in 71 patients with advanced pancreatic cancer.¹ In this study, VXM01 was safe and activated VEGFR2-specific cytotoxic T cells, which significantly improved patient survival.

References

1. Vaximm AG, an OSR Company, announces results from phase 2a trial of VXM01 and avelumab combination therapy in glioblastoma. News Release. Vaximm AG. March 27, 2025. Accessed April 4, 2025. https://www.biospace.com/press-releases/vaximm-ag-an-osr-company-announces-results-from-phase-2a-trial-of-vxm01-and-avelumab-combination-therapy-in-glioblastoma
2. VXM01 Plus Avelumab Combination Study in Progressive Glioblastoma. ClinicalTrials.gov. Updated October 20, 2022. Accessed April 4, 2025. https://clinicaltrials.gov/study/NCT03750071