VXM01 Plus Avelumab Shows Safety, Tolerability in Recurrent Glioblastoma

Glioma Cancer Tumor as malignant cells outbreak as a brain disease attacking neurons as a medical concept of neurological disease: © freshidea - stock.adobe.com

Among patients with recurrent glioblastoma (GBM), the combination of VXM01, an investigational oral anti–VEGFR-2 vaccine, and the PD-L1 inhibitor avelumab (Bavencio) was generally well tolerated, with safety and tolerability data consistent with prior findings for avelumab alone in this setting.¹

These findings come from an open-label, phase 2a trial (NCT03750071)² that is part of a collaboration with Vaximm AG and Merck KGaA, Darmstadt, Germany, assessing the combination’s safety and tolerability in GBM. According to the trial’s findings, most safety events were mild to moderate in severity and no additional safety signals for the combination of VXM01 and avelumab were observed.¹ VMX01 was not linked with any serious adverse events (SAEs), while 9 of 11 (81.8%) were related to the target disease.

In the nonresected cohort of patients, a 12.0% objective response rate (ORR) was observed—all partial remissions—and 4.0% had stable disease. In resected patients, the median overall survival (OS) ranged from 2.2 months to 46.5 months.

"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 glioblastoma," said Constance Hoefer, PhD, chief executive officer of Vaximm AG, in a press 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."

While the study only had 25 patients included, the observed median time to progression was 2.7 months (range, 0.3-22.1), and the median OS was 11.1 months (95% CI, 8.5-16.3; range, 3.8-38.2 months), which are both encouraging initial results for patients with recurrent GBM. Regardless of tumor size at baseline, decreased tumor size was observed in all responding patients

In addition, exploratory biomarker investigations found potential predictive and pharmacodynamic biomarkers of a VXM01-mediated tumor response. These promising, early safety and tolerability data support further studies of this combination in GBM.

About VXM01 and Its Mechanism of Action

VXM01 is an oral, live-attenuated bacterial vaccine engineered to express VEGFR2, inducing a targeted cytotoxic T-cell response. VXM01's T cells target and destroy VEGFR2-expressing cells within the tumor vasculature, disrupting blood supply and potentially enhancing immune cell infiltration.¹ Across tumors with VEGFR2 overexpression like GBM, VXM01 may also facilitate direct T-cell mediated tumor cell lysis.

Phase 1 data in 71 patients with advanced pancreatic cancer showed VXM01 to be safe and well tolerated. In this double-blind, randomized, placebo-controlled study, VXM01 led to the activation of VEGFR2-specific cytotoxic T-cells.¹ The agent also demonstrated promising clinical activity, including objective responses and survival benefits in recurrent GBM.¹

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 26, 2025. Accessed March 26, 2025. https://tinyurl.com/xxjxadre

2. VXM01 plus avelumab combination study in progressive glioblastoma. ClinicalTrials.gov. Updated October 20, 2022. Accessed March 26, 2025. https://www.clinicaltrials.gov/study/NCT03750071?cond=Glioblastoma&intr=VXM01&rank=2